A few days after the events of "Starcrushed", Marco is wallowing in despair over Star's departure from Earth. As his father Rafael calls the "Teen Sadness Hotline", his mother Angie suggests taking down the decorations from their end-of-school-year party, but Marco wants to leave them up in case Star returns.
Meanwhile, on Mewni, Star and her mother Queen Butterfly are on the run as Toffee continues to grow in power and magic continues to vanish from the universe. The two are on their way to a place called the "Sanctuary" to restore the members of the Magic High Commission, whose bodies have been reduced to floating balloons. Unfortunately, due to the interdimensional fritz, their warnicorn and carriage disappear, prompting them to set up camp for the night. When a patrol of Ludo's rat minions appears searching for them, Star is about to get rid of them with her magic wand. Queen Moon tells Star not to use magic, so Star fends them off with a stick.
While Star succeeds in fending off the rats, they cause the High Commission's bodies to float away and get stuck in a tree. Star and Moon climb the tree to recover their bodies, and Moon warns Star not to be so reckless while they're on the run. After retrieving the High Commission's bodies, Star and Moon arrive at the Sanctuary, where Moon communicates with a crocodile gatekeeper to let them inside. In the Sanctuary, Star places the High Commission's bodies in flower-shaped pods while Moon turns a valve to pour regenerative water on them from the well of magic. Unfortunately, because of the interdimensional fritz, all the water in the well has turned into sticky black sludge.
Unable to revive the Magic High Commission, Queen Moon resorts to her backup plan: having herself and Star remain in hiding at the Sanctuary with nothing to eat but corn snacks from a vending machine. Star is unhappy with hiding and wants to confront Toffee right away, but Moon says Toffee is too powerful and that he won't stop searching for them until he recovers his lost finger. Star is about to use her magic wand so Toffee can find them, saying she defeated him once and can do it again, but Moon reveals to her that Toffee and his monsters killed her mother.
Realizing the true extent of Toffee's evil, Star gives the magic wand to Moon and asks her to tell the story. Moon explains that, after her mother was killed, she turned to Eclipsa the Queen of Darkness out of desperation. Star believes that Eclipsa's been dead for a long time, but Moon says, "Eclipsa's alive, and I made a deal with her."
In a flashback, an army of monsters prepares to launch an attack on Butterfly Castle while a young Moon Butterfly mourns the death of her mother, the previous queen of Mewni. After Count Mildrew offers his condolences, the newly crowned Queen Moon is alerted to a situation in the castle meeting room: Mina Loveberry and the Magic High Commission are trying to coerce a confession of the monster army's captain for orchestrating the murder of Moon's mother. However, the monster captain insists that he and Moon's mother were about to sign a peace treaty when one of his generals—a monster known simply as "the Lizard"—went rogue and took half of the army for his own purposes.
One side of the royal court suggests declaring war on the monsters while the other side suggests signing the peace treaty, and a young River Johansen suggests letting Moon decide. However, Moon is unable to come to a decision in her time of grief and quickly leaves the meeting room. River catches up with her and apologizes for putting so much pressure on her shoulders, giving her a piece of "apology meat" before leaving. Moon returns to her chambers and finds Glossaryck in the book of spells crying over the death of Moon's mother. When Moon asks for Glossaryck's counsel, he doesn't offer much advice. He turns the book's pages to cry in Moon's mother's chapter, and the book turns to Eclipsa's forbidden chapter.
Moon goes to Rhombulus' crystal dimension and tells him to partially unfreeze the imprisoned Eclipsa. After he does so, the weak and tired Eclipsa begs Moon for a candy bar from the nearby vending machine. Moon gives a candy bar to Eclipsa, and she pulls her right hand—stained completely black—out of her glove to scarf it down. Seeing Moon's magic wand and very young age, Eclipsa deduces that the previous queen is dead. Moon asks Eclipsa to teach her a spell that can kill something immortal, and Eclipsa explains that such a spell requires a magical contract and comes with a price: Eclipsa's freedom. Moon accepts and takes Eclipsa by the hand, thus forging the contract between them. As soon as Eclipsa teaches Moon the spell, Rhombulus freezes her again.
Some time later, Moon goes to meet with the rogue monsters' general on the back of Lil Chauncey, and "the Lizard"—Toffee—appears before her. Moon tells Toffee and his monsters to leave Mewni or else. However, the monsters laugh at Moon's threat, telling her that they can regenerate from any wounds. Thus, Moon casts her "darkest spell"—the spell that Eclipsa taught her—causing black veins to appear on her arms. The spell severs the middle finger on Toffee's right hand, and he is unable to regenerate it. Realizing that Moon can mortally wound them, the monsters flee in terror, and Toffee walks off in defeat.
River congratulates Moon for driving the monsters away, but the High Commission condemn her for using forbidden magic. Nevertheless, Moon is determined to dissolve the remaining monster armies and protect Mewni as its queen. She returns to Butterfly Castle, and the members of her royal court bow to her in reverence.
At Ludo's monster temple in the Mewni mountains, his bald eagle and giant spider minions arrive with tacos from Earth. Ludo awakens from his sleep to find the temple in ruins and his wand's star fragment embedded in his right palm. Having no memory of the events in "Starcrushed" after Toffee took over his body, he seeks out Glossaryck and finds him trying to roast chocolate pudding over a fire. Glossaryck informs Ludo that he defeated the Magic High Commission, and Ludo is so pleased with himself that he decides to start writing a chapter about himself in the Book of Spells. The crystal in Ludo's hand beckons him toward Butterfly Castle, but he wants to write his chapter first.
Using a feather plucked from his head, Ludo prepares to write in the book, but Glossaryck tells him only the book's owner can write in it. Ludo believes he is the book's owner, but when he tries to write, the book takes on a life of its own and moves away from him. Ludo chases after the book, but it constantly evades him, tossing him into a stream and over a waterfall at one point. Eventually, Glossaryck gives Ludo the idea of using a spell, and Ludo tries casting Levitato on the book, but the energy feeds back and sends Ludo flying far into the distance.
After regaining consciousness on a beach of mermaids, Ludo makes his way back to the temple and demands an explanation for why he doesn't own the book anymore. Glossaryck jokingly suggests asking the book itself, but Ludo takes him seriously and tries to communicate with the book, apologizing for any misunderstanding between them. Glossaryck laughs at Ludo for failing to get the joke, and Ludo loses his patience and tosses the book into the fire.
At that moment, Toffee takes over Ludo's body again, and Glossaryck says he finally got what he wanted. As the book burns to ashes, Glossaryck himself starts to burn away as well; even though he knew this would happen, he is still a little surprised by it. Ludo regains control of his body as soon as Glossaryck disappears, and he mourns Glossaryck's apparent demise. Once again, the crystal in Ludo's hand beckons him toward Butterfly Castle, and he decides to take it over.
Some time after Star and Moon have gone into hiding, King Butterfly awakens in a messy castle and alone in bed. He turns on some dance music and kicks off a pumping dance party in the castle for himself and his subjects. The king and the citizens of Mewni party from sunrise to nightfall. The next morning, River wakes up, sees that Moon is still gone, and does the same thing all over again. However, his subjects are becoming tired of partying endlessly. By the following morning, River is only one in the castle with any energy to spare.
Using his dimensional scissors, Marco appears on Mewni to see Star and give her some of her favorite Earth cereal. River happily greets Marco, and Marco asks if Star is in trouble after leaving Earth so suddenly. River assures him that Star is just fine and that she and her mother left on a little trip, leaving him to look after the castle and keep up the people's morale. However, Marco shows River that the people of Mewni are in a state of panic.
On the castle balcony, River addresses the people and asks if they are satisfied with his leadership after Star and Moon have left. The people complain about the large amounts of garbage piling up, the buildings that are on fire, and the giant monster in the Mewman cornfields. River shouts at the monster to leave, but the monster—unable to hear River from so far away—approaches the village and starts stomping on everything. The people's faith in River drops even lower, and River loses confidence in himself as a king.
River goes back inside the castle and sinks into despair, admitting that he has no idea where Star and Moon went or when they'll return. Marco tells him that they cannot return home if they have no home to return to and that River must lead his people. Inspired by Marco's words, River addresses his subjects again and tries to rally them together to face the stampeding monster. The people still doubt River's ability to rule, but River accepts this and says he's all they have and they're all he has. He says further that they don't need magic to do extraordinary things and that everyone can do something unique and helpful. The people are inspired by River's words and join him in challenging the monster.
Marco, River, and the people of Mewni confront the monster stomping through the village and tell him to leave. However, the reason for the monster's attack turns out to just be the result of a failure to communicate; he thought River was calling him to approach, not leave. With that cleared up, the monster leaves as he's told, and the people celebrate over their victory. River decides to hold one last party at the castle in his subjects' honor, and they cheer his name. Unfortunately, Ludo suddenly appears to join in the cheering, and he launches his own monster invasion on Mewni.
Back at the Sanctuary, Star and Moon wake up to discover that the black sludge in the well of magic is overflowing and flooding everything. Unable to recover the High Commission's bodies from their pods, Star and Moon escape from the Sanctuary just before it sinks into the sea. To make matters worse, all of Moon's magic is now gone. As they evade another patrol of Ludo's rats, Moon seizes Star's wand before she can use it, and they try to figure out another hiding place. When Star hears a frog croaking nearby, she gets an idea.
Star takes her mother to Buff Frog's house, where Buff Frog happily welcomes them. Moon is uncertain about taking shelter in a monster's home, especially one that used to work for Ludo, but she accepts that over dealing with the dangers of the forest. Inside Buff Frog's mud-filled home, Star is greeted by his growing tadpole children, but Moon is disgusted by everything she sees. When Buff Frog informs Star and Moon that Ludo has taken over Butterfly Castle, Star worries about her father, but Moon is more concerned about keeping Star safe. As Moon excuses herself to freshen up, Star asks Buff Frog to keep her distracted while she goes to destroy Toffee, and Buff Frog agrees.
When Moon returns, Buff Frog suggests they pass the time by playing a board game while Star hangs out with the tadpoles in their bedroom. Buff Frog looks through a bunch of his board games (all of which favor monsters over Mewmans) before settling on one called Puddle Defender. As the game gets underway and Star sneaks around behind Moon's back, Moon realizes that the game is biased toward monsters, and Buff Frog accuses Moon of being biased toward Mewmans. When Moon goes too far in insulting Buff Frog, he assures her that just as she would do anything to protect Star, he would do anything to protect his tadpoles. For that reason, he refuses to cover for Star any longer and locks down all the exits in his home so Star can't escape.
Star locks herself inside the tadpoles' room, furious by her mother's cowardice and Buff Frog's betrayal. Just then, Katrina speaks up, revealing that she can talk, and she and the tadpoles offer to help Star escape the house. When Katrina asks Star what her plan is to defeat Toffee, Star reveals that she doesn't have a plan and intends to improvise. Despite this, Star sets out for Butterfly Castle, and Katrina comments to her siblings that Star might perish.
Back at Butterfly Castle, Ludo and his minions are removing every trace of the Butterfly family from the castle to make room for Ludo's beginning reign. Outside, one of the Mewmans tries to sell "King Ludo" merchandise but has little success because no one in the kingdom likes Ludo, much to his dismay. Ludo goes to the castle dungeons, where Marco and River are chained up, and demands that River help him make the people like him. River refuses, so Ludo gives him 24 hours to change his mind or else he'll use Levitato to send him into the sky forever. After securing the dungeon key around his neck (having to use butter to fit it around his large head), Ludo leaves.
When Ludo accidentally leaves the butter behind, Marco grabs it with his foot and uses it to slip out of his chains. Before River can do the same thing, he eats the butter, so Marco is forced to steal Ludo's key to free him. As Marco escapes through the air conditioning vents to the royal bedroom, he meets Ruberiot, the royal jester Foolduke, and a mime girl; they have gone into hiding since Ludo's takeover and help themselves to his stuff whenever he isn't around. When Ludo returns to the bedroom to sleep, the four hide in the vents. Marco tries to convince Ruberiot and the others to help him steal Ludo's key, but they refuse out of an unwillingness to "do stuff". When Marco's words of inspiration fail to motivate them, he expresses his contempt for them before setting out on his own.
Marco sneaks into the royal bedroom and tries to steal the key around Ludo's neck. Just before he is caught, Ruberiot, Foolduke, and the mime girl appear and pretend to entertain Ludo with a song dedicated to him. Marco tries to seize the key while Ludo is distracted, but the performers start to argue over artistic differences, and they and Marco eventually have to retreat. Luckily, Foolduke had seized the key during the confusion.
Marco returns to the dungeons to free River, but River refuses to abandon his subjects. When Marco hears Ludo approaching, he chains himself back up and drops the key. With River's 24 hours up, Ludo recovers the key and demands River's assistance again. Once again, River refuses, and Ludo and his minions drag him away. As punishment for his defiance, River is publicly banished from Mewni when Ludo casts Levitato to hurl him into the sky. Having witnessed this from the sewers, Ruberiot and the others wonder what to do now, and Marco says it's time to fight back.
Some time after Ludo has seized the Mewni royal throne, he orders a choir of Mewman children to sing songs in his honor but tosses them into the sky when they sing off-key. By this time, Ludo has assumed complete control of the village and commanded the people to worship him. On his way to the throne room, Ludo gets ambushed by a person in a rat costume. The person in the costume reveals themself to be Star Butterfly, who demands to know where her father is. However, Star is quickly captured by Ludo's spider, and following his wand's orders, Ludo has her imprisoned in the dungeons. As Star is carried away, she warns Ludo that Toffee is controlling him through his wand.
After Star is imprisoned in the dungeons, another person in a rat costume appears outside the dungeon doors and knocks out the rat guard. This person enters Star's dungeon cell and reveals themself to be Marco, much to Star's delight. Marco frees Star from her chains, and the two reunite with a warm hug. Marco tells Star what happened to her father and introduces her to the resistance movement consisting of himself, Ruberiot, Foolduke, and the mime girl. Together, the five come up with a plan of ruining Ludo's credibility, but Star says they need to get rid of Toffee. Just then, Ludo enters the dungeon cell and discovers the five hatching a plan. Marco, Ruberiot, Foolduke, and the mime girl are captured while Ludo drags Star away with Levitato.
On one of the castle balconies, Ludo continues his earlier conversation with Star about the wand in his hand, and Star reveals that Toffee is inside the wands. As Ludo wonders how to get him out, Star recalls the last time she faced him and comes up with an idea. She takes Ludo by the hand and starts casting the Whispering Spell.
Meanwhile, Buff Frog and Queen Moon appear to break Marco out of the dungeon (leaving Ruberiot, Foolduke, and the mime girl behind), and Buff Frog carries the three of them up to a castle balcony adjacent to the one Star and Ludo are on. When Moon realizes that Star cast the Whispering Spell, she yells at Star to get away, but it's too late. Just like in "Storm the Castle", the wand fragment in Ludo's hand begins releasing massive power and explodes, reducing that part of the castle to a crater. Buff Frog carries Marco and Moon down to the crater, where they discover only Ludo's body with pink glowing eyes. Star appears floating in a pool of black sludge with small globs of gold, and her voice comes out of Ludo's mouth when she speaks. Star is unsure of where she is, but Moon assures her that they'll find her.
All of a sudden, the connection between Star and her loved ones starts to break up, and the giant form of Toffee appears out of the black sludge that Star is swimming in. Toffee explains that the sludge is all the magic he drained from the universe and corrupted, with only small gold traces of uncorrupted magic remaining. Toffee reassumes control of Ludo's body and demands his finger back in exchange for Star. Despite Star's unheard protests, Moon gives Toffee his severed finger. As the finger binds to Toffee's hand, Toffee leaves Star behind in the wellspring of corrupted magic, and his body completely regenerates. He spits out Ludo's body and crushes the drained wand crystal to dust. When Moon and Marco demand to know where Star is, Toffee tells them she's dead and walks away.
Distraught by her daughter's supposed death, Moon loses her temper. As her cheek diamonds turn black and the black veins on her hands crawl further up her arms, she attacks Toffee in a blind rage. However, Toffee dodges and catches all of her punches. Using Star's wand, Moon attempts to cast her darkest spell on him again, but all of the wand's magic is gone. Marco, equally upset by Star's death, punches a hole straight through Toffee's chest, but Toffee instantly regenerates and tosses Marco aside. After immobilizing Moon as well, Toffee leaves. Ludo grabs him by the leg and asks if he had any part to play in all of this, and Toffee cruelly answers "no" before walking off.
Back in the pool of black sludge, Star swims around helplessly until she discovers one last piece of untouched magic still floating in the well. She desperately swims toward it and dives far below the surface of the water to seize it, but she runs out of air and starts to drown. Meanwhile, in the outside world, Queen Moon tries to reassemble the pieces of the wand in a last-ditch effort to bring Star back, all while crying tears of sorrow.
In an unknown pitch-black space, Star wakes up to find Glossaryck making stew in a cauldron. In this strange place that even Glossaryck doesn't know, Star believes she's dead. Since there's nothing to do about her situation, Glossaryck tells her to eat some stew, but Star refuses as long as Toffee is still terrorizing her friends and family. Suddenly, the small piece of magic appears inside the stew, and Star believes Glossaryck is just playing another of his mind games to teach her a lesson. She "dips down" into the stew to grab the last piece of magic, and it releases tremendous magical energy to give birth to another wand-powering unicorn.
At the Sanctuary, the black sludge suddenly turns gold, and the Magic High Commission's bodies appear out of their pods. The wand in Queen Moon's hand raises into the sky, bursts into pieces, and reassembles to form a brand new magic wand. Star suddenly emerges from the wellspring and takes on a new mewberty form with six arms and brilliant gold butterfly wings. With her upgraded wand, Star takes aim at Toffee and shoots him with an obliterating blast of magic that reduces him to bones and melted flesh. Star collapses with exhaustion, and Marco, Moon, and Buff Frog rush over to greet her, overjoyed that she's alive.
Toffee crawls toward Star and her friends, laughing and still confident that he's won, but Ludo finishes him off by dropping a stone pillar on him. As Star, Marco, and Buff Frog wonder if Toffee's truly been destroyed, Queen Moon feels pain from the black veins on her arms and runs off. Ludo asks Star to use his dimensional scissors and throw him into the void again, saying he needs to do some soul-searching. After Ludo sets his eagle and spider minions free, Star throws Ludo into the void with a bag of Gold'n Crispz and wishes him good luck. Finally, all the people that Ludo sent away with Levitato, including King River, return to Mewni on the backs of eagles.
In the final scene, Moon races to Eclipsa's crystal prison and is relieved to see that she's still imprisoned. However, when Moon walks away, Eclipsa's crystal prison starts to crack.
- The 100 Acre Avatar League, The Justice Acre Wood Brood, Ash Ketchum, Pikachu, Misty, Togepi, Brock, Serena, Fennekin, Littlefoot, Cera, Ducky, Petrie, Spike, Chomper, Ruby, Guido, Grandpa Longneck, Grandma Longneck, Simba, Nala, Timon, Pumbaa, the Mighty Morphin Power Rangers, Winston Steinburger, Dudley, Hampton, Harley Diaz, Rachel Diaz, Ethan Diaz, Daphne Diaz, Georgie Diaz, Lewie Diaz, Beast Diaz, Serena and the Sailor Scouts, Scooby-Doo, Shaggy Rogers, Fred Jones, Daphne Blake, Velma Dinkley, The DigiDestined and their Digimon, Squire Flicker, Princess Flame, King Allfire, Queen Griddle, Sir Loungelot, Sir Blaze, Sir Burnevere, Sir Galahot, Sir Hotbreath, The Wandering Minstrel, Cinder and Clinker, Kazuto Izuka, Narue Nanase, Masaki Maruo, Hajime Yagi, Kanaka Nanase, The Bowser family, Psycho Rangers, Dr. Facilier, Scar, The Dazzlings, Kurumi Tokisaki, Attila and Hun, Megan, Nora Beady, Denzel Crocker, Vicky, Foop, Dark Laser, Norm the Genie, Head Pixie, Sanderson, Lord Zedd, Rita Repulsa, Goldar, Hunter J, Kyoko Kudo, Yuki Kashiwazaki, Aya Kanazawa, The Grand Duke of Owls, Pam the Destroyer, The Crime Empire (Joker, Harley Quinn, Penguin, Two-Face, Negaduck, Quackerjack, Megavolt, Bushroot, and The Liquidator), and Team Rocket guest stars in this film.
- The Bowser family, Psycho Rangers, Dr. Facilier, Scar, The Dazzlings, Kurumi Tokisaki, Attila and Hun, Megan, Nora Beady, Denzel Crocker, Vicky, Foop, Dark Laser, Norm the Genie, Head Pixie, Sanderson, Lord Zedd, Rita Repulsa, Goldar, Hunter J, Kyoko Kudo, Yuki Kashiwazaki, Aya Kanazawa, The Grand Duke of Owls, Pam the Destroyer, The Crime Empire and Team Rocket will work for Ludo/Toffee.
- The Weekenders, The Jungle Book, Pinocchio, The Lion King, Stuck in the Middle, The Princess and the Frog, Drawing Duck and Star vs. the Forces of Evil: The Battle for Mewni were all made by Disney.
- Jason Marsden as Tino Tonitini
- Grey DeLisle as Lor McQuarrie
- Phil LaMarr as Carver Descartes
- Kate Soucie as Tish Katsufrakis
- Rebecca Shoichet as Sunset Shimmer
- Tara Strong as Sci-Twi
- Cathy Weseluck as Spike the Dog
- Ali Liebert as Juniper Montage
- Josh Grelle as Shido
- Michelle Rojas as Tohka
- Bryn Apprill as Kotori
- Tia Ballard as Yoshino
- Michelle Lee as Origami
- Felecia Angelle as Mana
- Carly McKillip as Sakura Kinomoto
- Mona Marshall as Doraemon
- Johnny Yong Bosch as Noby Nobi
- Cassandra Morris as Sue/Leo and Luna
- Brian Beacock as Sneech
- Kaiji Tang as Takeshi "Big G" Goda
- Jim Cummings as Buzzie the Vulture
- Jeff Bennett as Flaps the Vulture/Zazu/Petrie
- Baron Davis as Dizzy the Vulture
- Jess Harrell as Ziggy the Vulture
- Joe Ochman as Jiminy Cricket
- Patrick Warburton as Kronk
- Justin Nimmo as Zhane the Silver Ranger
- Janet Varney as Korra
- David Faustino as Mako
- P.J. Byrne as Bolin
- Seychelle Gabriel as Asami Sato
- Tara Strong as Timmy/Poof
- Daran Norris as Cosmo
- Susanne Blakeslee as Wanda
- Chris Hardwick as Otis
- Jeff Garcia as Pip
- Leigh-Allyn Baker as Abby
- Tino Insana as Pig
- Cam Clarke as Freddy
- Rob Paulsen as Peck
- Grant Palmer as Linclon
- Catherine Taber as Lori
- Liliana Mumy as Leni
- Nika Futterman-Frost as Luna
- Cristina Pucelli as Luan
- Jesica DiCicco as Lynn/Lucy
- Grey DeLisle as Lana/Lola/Lily/Daphne Blake
- Lara Jill Miller as Lisa
- Ashleigh Ball as Rainbow Dash/Applejack
- Andrea Libman as Pinkie Pie/Fluttershy
- Tabitha St. Germain as Rarity
- Caitlin Murphy as Ronny Robinson/Yellow Ranger
- Bob West as Barney
- Patty Wirtz as BJ
- Julie Johnson as Baby Bop
- Michaela Dietz as Riff
- Candace Cameron-Bure as D.J Tanner
- Kari Wahlgren as Chloe Carmichael
- Veronica Taylor as Ash Ketchum/Narue Nanase
- Ikue Ōtani as Pikachu
- Haven Burton-Paschall as Serena
- Rachael Lillis as Misty/Kanaka Nanase
- Satomi Kōrogi as Togepi
- Eric Stuart as Brock
- Scott McAfee as Littlefoot
- Candace Hutson as Cera
- Heather Hogan as Ducky
- Rob Paulsen as Spike
- Jamie McGonnigal as Kazuto Izuka
- Jimmy Zoppi as Masaki Maruo
- Michele Knotz as Hajime Yagi
- Frank Welker as Scooby-Doo/Fred Jones
- Casey Kasem as Shaggy Roggers
- Grey DeLisle as Daphne Blake
- Mindy Cohn as Velma Dinkley
- Terri Hawkes as Serena/Sailor Moon
- Karen Bernstein as Amy/Sailor Mercury
- Katie Griffin as Raye/Sailor Mars
- Susan Roman as Lita/Sailor Jupiter
- Stephanie Morganstern as Mina/Sailor Venus
- Joshua Seth as Taichi "Tai" Kamiya
- Tom Fahn as Agumon
- Michael Reisz as Yamato "Matt" Ishida
- Kirk Thornton as Gabumon
- Colleen O'Shaughnessey as Sora Takenouchi
- Tifanie Christun as Biyomon
- Mona Marshall as Koushiro "Izzy" Izumi
- Jeff Nimoy as Tentomon
- Philece Sampler as Mimi Tachikawa
- Anna Garduno as Palmon
- Michael Lindsay as Joe Kido
- R. Martin Klein as Gomamon
- Wendee Lee as Takeru "T. K." Takaishi
- Laura Summer as Patamon
- Lara Jill Miller as Hikari "Kari" Kamiya
- Edie Mirman as Gatomon
- Mac Heywood as Winston Steinburger
- Ryan Belleville as Dudley
- Matt Baram as Hampton
- Jenna Ortega as Harley Diaz
- Ronni Hawk as Rachel Diaz
- Isaak Presley as Ethan Diaz
- Ariana Greenblatt as Daphne Diaz
- Kayla Maisonet as Georgie Diaz
- Nicolas Bechtel as Lewie Diaz
- Malachi Barton as Beast Diaz
- Edward Glen as Squire Flicker
- Stephanie Morgenstern as Princess Flame
- Aron Tager as King Allfire
- Steven Sutcliffe as Queen Griddle
- Juan Chloran as Sir Loungelot
- Richard Binsley as Sir Blaze/The Wandering Minstrel
- John Stocker as Sir Burnevere
- Richard Waugh as Sir Galahot/Cinder and Clinker
- Dan Hennessey as Sir Hotbreath
- Billy West as Geeker
- Lady MacBeth as Cree Summer
- Brad Garrett as Noah
- Jim Cummings as Darkwing Duck
- Estelle as Garnet
- Michaela Dietz as Amethyst
- Deedee Magno-Hall as Pearl
- Eden Sher as Star Butterfly
- Adam McArthur as Marco Diaz
- Michael C. Hall as Toffee
- Alan Tudyk as Ludo/River Butterfly
- Sonny Ashbourne Serkis as Young River
- Artt Butler as Mr. Diaz
- Nia Vardalos as Mrs. Diaz
- Grey DeLisle as Moon Butterfly
- Katie Driver as Young Moon
- Amy Sedaris as Mina Loveberry
- Zosia Mamet as Hekapoo
- Kevin Michael Richardson as Rhombulus
- Fred Tatasciore as Buff Frog
- Esmé Bianco as Eclipsa Butterfly
- Natalie Palamides as Foolduke
- Patrick Stump as Ruberiot
- Jeffrey Tambor as Glossaryck
- Kazumi Evans as Adagio Dazzle
- Marÿke Hendrikse as Sonata Dusk
- Diana Kaarina as Aria Blaze
- Alexis Tipton as Kurumi Tokisaki
- Robert Axelrod as Lord Zedd
- Machiko Soga as Rita Repulsa
- Kerrigan Mahan as Goldar
- Keith David as Dr. Facilier
- Sonny Dey as Pokémon Hunter J