In 3067 BC, the Scorpion King leads his army on a campaign to conquer the world. Seven years later, the Scorpion King and his army are defeated and exiled to the desert of Ahm Sher. His men die of heat exhaustion, leaving only the Scorpion King. Vowing to give Anubis his soul for the power to defeat his enemies, an oasis is created to hide the Scorpion King's pyramid and giving him a legion of humanoid jackal warriors to seek revenge. The Army of Anubis sweeps across Egypt, destroying everything in its path, but once their task is finished Anubis claims the Scorpion King's soul and his army.
In 1933, the TARDIS Team acompanied by The Human Mane 5 join Rick and Evelyn O'Connell in exploring a ruined mortuary structure in the ancient Egyptian city of Thebes with their son, Alex. They find the Bracelet of Anubis. In London, Alex puts on the bracelet, which shows him a vision with directions to the Oasis of Ahm Shere. Alex has seven days to reach the oasis, or the bracelet will kill him the moment the sun's rays shine on the Scorpion King's pyramid; at that point, the Scorpion King and his army will reawaken.
Evelyn and Dr. Aaron are captured by an Egyptian cult who have resurrected Imhotep; they wish to use Imhotep's power to defeat the Scorpion King, which would give him command of Anubis' army to take over Earth. The cult, led by Baltus Hafez, the British Museum's curator, includes a warrior named Lock-Nah and Meela Nais, the reincarnation of Imhotep's love Anck-su-namun. The O'Connells and our heroes set out to rescue her, accompanied by Evelyn's brother Jonathan, the NEXO Knights and the Medjai Ardeth Bay.
After having discovered the bracelet is missing, they attempt to kill Evelyn and the Zeroth Doctor, however a fight ensues between Rick and Imhotep. Imhotep then calls on the help of his mummified soldiers to kill them. After freeing Evelyn they flee on a double-decker bus. After defeating them, Alex, Wave the Swallow, Cynder, Robin Underwood, Human Applejack, Human Rarity, and Human Fluttershy are kidnapped and they travel across Egypt to rescue them along with Rick's associate from his past adventures, Izzy, a pilot, who provides the group with transportation. (While Dr. Aaron and his crew travel in the TARDIS.) In the third of a train, Alex, Wave, Cynder, Robin, Human Applejack, Human Rarity, and Human Fluttershy are pushed by Imhotep and are confronted by Saruman, Jestro, the Book of Monsters, Mirage, Lord Business, Lord Dragaunus, and Mumm-Ra. They tell them that they been sent by the Dark Master to to awaken Imhotep.
The bracelet gives Alex visions, directions to Ahm Shere that the cult follows. At each location, Alex leaves clues for his parents and their friends who follow in the TARDIS and Izzy's dirigible. Imhotep uses the Book of the Dead to give Meela Nais the soul of Anck-su-namun but by doing so he allows Evelyn to unlock the memories of her previous life as Princess Nefertiri, the bracelet's keeper and Pharaoh Seti I's daughter. Lock-Nah discovers that Alex has been leaving clues, so Imhotep makes a wall of water that attacks the dirigible and the TARDIS. The heroes and the O'Connells crash in the jungle of Ahm Shere. Izzy stays with the dirigible in hopes of repairing it while Ava Prentis stays behind to look after the TARDIS and help Izzy repair his dirigible. The heroes and the O'Connells attack the cult, and both groups are attacked by pygmy mummies. Rick retrieves Alex while Ardeth Bay kills Lock-Nah. Wave, Cynder, Robin, Human Applejack, Human Rarity, and Human Fluttershy are rescued by Dr. Aaron, Human Pinkie Pie and Human Rainbow Dash. They escape from the pygmies, who kill most of the cult except for Baltus. Imhotep and Anck-su-namun are unharmed due to Imhotep's powers and Anck-su-namun being the keeper of the Book of the Dead.
Rick and Alex run to the pyramid, barely making it before sunrise. The bracelet detaches from Alex's arm. Ardeth regroups with the Medjai in case Anubis' army rises. Anck-su-namun stabs Evelyn and kills her. Rick, grieving, pursues Imhotep. Baltus puts on the bracelet and revives the army. As Imhotep walks into the pyramid, Anubis takes his powers, wanting Imhotep to fight as a mortal. Rick and the TARDIS Team find Imhotep, Saruman, Jestro, the Book of Monsters, Mirage, Lord Business, Lord Dragaunus, and Mumm-Ra summoning the Scorpion King and they fight. The Medjai engage the army. The Scorpion King interrupts Rick and Imhotep, the heroes and villains' fight. Dr. Aaron and his crew realize that the Scorpion King is Mathayus. Imhotep tells the Scorpion King that he is the Scorpion King's slave, but Rick was sent to kill him. During Rick and the Scorpion King's fight, Baltus is killed. Jonathan, Alex, Batty Koda, Robin, and The Human Mane 5 collaborate to steal the Book of the Dead from Anck-su-namun. Alex uses the book to resurrect Evelyn, who duels with Anck-su-namun. In a direct reference to the first film, Alex asks Jonathan for help to decipher a hieroglyph; the same hieroglyph Evelyn had to translate for Jonathan in first film.
The Human Mane 5, Batty Koda, Robin, Alex and Jonathan go help Rick while Evelyn fights Anck-su-namun. It is revealed that the scepter that Jonathan has been carrying extends into a spear that can kill the Scorpion King. The Medjai seemingly defeat Anubis' army despite heavy casualties, but see that they have only defeated the vanguard, and the full army is charging towards them. However, before the Anubis warriors hit the Medjai lines, Rick succeeds in killing the Scorpion King, sending him and his army back to the Underworld. The Scorpion King's death breaks his oath with Anubis, causing the oasis to turn back into a desert, and the oasis to be sucked into the pyramid. Rick and Imhotep are hanging from the edge of a pit that leads into the underworld. Evelyn risks her life to save Rick, but Anck-su-namun refuses to do the same for Imhotep, and abandons him. Heartbroken about her desertion, he lets go of the ledge, falling into the underworld, to his death. Anck-su-namun, running away from the pyramid, falls into a pit of scorpions and flesh-eating scarab beetles.
The heroes and the O'Connells reach the top of the pyramid, which is being sucked into the desert. Izzy arrives with a modified dirigible and saves the O'Connells. While Ava arrives with the TARDIS and Dr. Aaron, his crew, The Human Mane 5, and the NEXO Knights bored it. Jonathan grabs the diamond at the top of the pyramid. Ardeth Bay salutes them as they fly over him.