After a failed attempt to rescue his first mate, Joshamee Gibbs in London, Captain Jack Sparrow is brought before King George II. The king wants Jack to guide an expedition to the Fountain of Youth before King Ferdinand and the Spanish Navy can locate it. Jack’s old nemesis, Captain Hector Barbossa, now a privateer in service to the British Navy after losing his leg and ship, the Black Pearl, which he says was sunk, is heading the expedition.
Jack refuses the offer and escapes. He meets up with his father, Captain Teague, who warns Jack about the Fountain’s rituals. Jack learns someone is impersonating him to recruit a crew to find the Fountain. The impostor is Angelica, Jack’s former lover, and the daughter of the ruthless pirate Blackbeard, who practices voodoo magic and wields the mythical “Sword of Triton” that controls his ship, the Queen Anne’s Revenge. While Jack is shanghaied aboard Blackbeard’s ship, Gibbs escapes execution by memorizing and destroying Jack’s map showing the Fountain’s location, forcing Barbossa to take him along.
Meanwhile, after a failed mutiny aboard the Queen Anne’s Revenge, Jack is forced to guide the crew to the Fountain. Blackbeard seeks the Fountain’s power to circumvent his predestined fatal encounter with a “one-legged man”, who happened to be Barbossa. Jack must find two silver chalices aboard Juan Ponce de León’s missing flagship, the Santiago. The Fountain’s water must simultaneously be drunk by two people from the chalices. Drinking from one chalice containing a mermaid’s tear will extend life; the second person dies, their remaining years of life transferred to the other drinker. Jack also discovers that the Black Pearl was captured and shrunk before being added to Blackbeard’s collection of other shrunken ships in bottles.
The Queen Anne’s Revenge heads for Whitecap Bay to find and harvest mermaid tears. A mermaid named Syrena is caught, but Philip Swift, a captive missionary, falls in love with her. Reaching Ponce de León’s ship on an uncharted island, Angelica and Blackbeard coerce Jack into retrieving both chalices. Jack locates the grounded, decaying vessel, only to find Barbossa there. Both guess that the Spanish have taken the chalices, after they are nowhere to be found on the vessel.
Jack and Barbossa team up to sneak into the Spanish camp and steal the chalices. Barbossa reveals he only wants revenge against Blackbeard for attacking the Black Pearl, and his leg being amputated. Jack and Barbossa escape with the chalices. Meanwhile, Syrena, reciprocating Philip’s love, is tricked into shedding a tear. Blackbeard collects it, leaving her to die while Philip is forced to go with them. Jack returns with the chalices and bargains with Blackbeard for Angelica’s safety, Jack’s confiscated magical compass, and Gibbs’ release. In return, Jack vows to give Blackbeard the chalices and lead him to the Fountain; Blackbeard agrees, and Gibbs is set free with the compass.