In order to control the oceans, Lord Cutler Beckett executes anyone associated with piracy by ordering Davy Jones to destroy all pirate ships in the seas. Condemned prisoners sing "Hoist the Colours" to compel the nine Pirate Lords to convene at Shipwreck Cove to hold the Brethren Court. Because Captain Jack Sparrow, Pirate Lord of the Caribbean Sea, never named a successor before being killed, Captain Barbossa, along with Will Turner, Elizabeth Swann, Tia Dalma, and the crew of the Black Pearl, plot to rescue Jack from Davy Jones' Locker. Traveling to Singapore, the crew meet Captain Sao Feng (Pirate Lord of the South China Sea), who owns navigational charts to the Locker and quickly gains an unpredictable interest in Elizabeth. Beckett's soldiers invade, but the crew escape. Feng and Turner make a deal to give Jack to Feng, so he in turn can use the Pearl to rescue his father Bootstrap Bill Turner from the Flying Dutchman. The crew travels to the locker and rescues the marooned Jack. They find themselves trapped, encountering dead souls, including Elizabeth's father Governor Swann who was executed by Beckett. Tia Dalma reveals that the Goddess "Calypso" charged Davy Jones with the job to guide the souls of those who died at sea to the next world. Once every ten years he could come ashore to be with the woman he loved. But he corrupted his purpose and was cursed to become a monster. The soul of Governor Swann reveals that the Dutchman must always have a captain.
Returning to the living world, the Pearl stops at an island for fresh water, where the crew find the Kraken lying dead on the beach, having been killed by Jones under orders from Beckett. They are then attacked by Sao Feng and Beckett's men. Through a complex series of deals, Elizabeth is handed over to Feng, who believes she is the goddess Calypso, while the rest of the crew make for Shipwreck Cove aboard the Pearl, though Jack later throws Will off the ship as part of the plan to seize control of the Dutchman. Sao Feng tells Elizabeth that the first Brethren Court bound Calypso in human form after she betrayed her lover, Davy Jones. He plans to release her to defeat Beckett. Davy Jones attacks Feng's ship, the Empress, mortally wounding Feng in the process, but he appoints Elizabeth his successor as Pirate Lord before dying. Elizabeth and the crew are locked in the brig of the Dutchman and she finds Bootstrap Bill Turner merging with the side of the ship and losing his mind. In a moment of clarity Bootstrap reveals that whoever kills Davy Jones must take his place, bound to serve the Dutchman forever. He reiterates that "the Dutchman must always have a captain." Admiral Norrington frees Elizabeth and her new crew from the Dutchman, but is killed by a crazed Bootstrap Bill.
The Black Pearl arrives at Shipwreck Cove where Barbossa attempts to persuade the Brethren Court to release Calypso. Davy Jones visits Tia Dalma in the Pearl's brig, revealing she is Calypso, and they promise to be together again. Jack's father Captain Teague and Keeper of the Pirate Code, informs the Court that only an elected Pirate King can decide on going into battle. A vote is taken. To avoid a stalemate, Jack casts his vote for Elizabeth, making her King.
The Brethren Court and Beckett's fleets emerge for war. On a sandbank, Elizabeth, Jack, Barbossa, Beckett, Jones, and Will parley, trading Will for Jack, and Barbossa steals Jack's piece of eight, all of which are owned by the Pirate Lords and required to free Calypso. Barbossa frees Calypso, but when Will reveals it was Jones who made it possible for the first Court to imprison her, Calypso vanishes and summons an enormous maelstrom.
The Pearl and the Dutchman battle in the maelstrom. Elizabeth and Will are wed by Barbossa before swinging over to the Dutchman to aid Jack. On board the Dutchman, Jones and Jack engage in a duel, with Jones gaining the upper hand. Jones stabs Will with a sword, causing Bootstrap to fly into a rage and attack Jones. Jones begins to gain the upper hand, but Jack and Elizabeth help Will stab Jones' heart. Jones falls into the maelstrom, while Will succumbs to his injuries. Jack and Elizabeth escape the Dutchman as it is sucked into the maelstrom, while the crew of the Dutchman converge on Will, led by Bootstrap.
As Beckett's ship, the Endeavour, approaches to destroy the Pearl, the Dutchman rises, now captained by Will, and the crew free of Jones' curse. Together, the two pirate ships destroy the Endeavour, with a stunned Beckett going down with the ship while his navy retreats, demoralized by the loss of both the Endeavour and their commander in Beckett. With Will now forever bound to escort souls lost at sea to the next world, he and Elizabeth bid farewell to each other on the beach of an abandoned island. Will departs on the Dutchman, leaving Elizabeth pregnant and with the chest containing his heart.
Jack and Joshamee Gibbs discover Barbossa has stolen the Black Pearl again, but Jack planned ahead and cut out Sao Feng's navigational charts, departing from Tortuga alone to track down the mythical Fountain of Youth to become immortal.
- Peter Griffin, Belle, Blythe Baxter, Zoe Trent, Pepper Clark, Penny Ling, Vinnie Terrio, Sunil Nevla, Minka Mark, Russell Ferguson, Mitzi, Buttercream Sunday, Roger Smith, Bender Bending Rodríguez, Minerva Mink, Judy Hopps, and Nick Wilde guest star in this film.
- The Dazzlings and Ernie the Giant Chicken will work for Davy Jones in this film.
- Beauty and the Beast, Zootopia, and Pirates of the Caribbean: At World's End are Disney films.
- The storyline continues in Brian and the Eeveelution Family's Adventures of Pirates of the Caribbean: On Stranger Tides.