The film opens with Elizabeth Swann singing Yo Ho (A Pirate's Life for Me) while the HMS Dauntless sails through the Caribbean Sea. As a child, Elizabeth often fantasizes about pirates and life at sea. This fantasy was shown while Elizabeth and her father, Governor Weatherby Swann, sailed aboard the Dauntless en route to Port Royal. It was during this voyage that Elizabeth met Will Turner, who is pulled from the sea drifting amidst the murdered crew and burning wreckage of a British ship attacked by pirates. On that day, Elizabeth takes from the unconscious Will a souvenir a medallion bearing the skull of a pirate's Jolly Roger hoping to save his life, fearing it marked him as a pirate. Moments later, while looking at the medallion, Elizabeth caught a brief glimpse at a mysterious ship with black sails with a flag with the same skull as the medallion slipping into the mist. This event sets the whole story in motion.

The story continues eight years later, when Elizabeth awakens from dreaming the aforementioned events. As she takes out the medallion and puts it on, her father comes in bearing a gift: a new dress. Governor Swann then expressed his hope that Elizabeth would accompany him to the promotion ceremony for James Norrington, a respected Royal Navy officer who accompanied the two during the Dauntless' voyage. Although Elizabeth loved the dress, she did express that "women in London must've learned not to breathe". It was then that Governor Swann met with a visitor: Will Turner, now a common blacksmith who presented his order of a ceremonial sword for Norrington. Will loves Elizabeth, but he knew his place and kept his feelings deeply hidden, much to Elizabeth's displeasure. Governor Swann, meanwhile, desires that his daughter be betrothed to Commodore James Norrington, a marriage which would have brought her wealth and respect. After the ceremony, Norrington proposed to Elizabeth. But while Norrington proposed, Elizabeth, whose tightly laced corset nearly suffocated her, faints and falls off a rampart and into the bay. Her unlikely rescuer is the infamous Captain Jack Sparrow, newly arrived in Port Royal to commandeer a ship. Despite his gallant actions, Jack is promptly jailed for piracy and sentenced to hang, against Elizabeth's protests. However, Elizabeth changed her mind when Jack threatened her so he could escape, though was later captured again.

That night, Elizabeth read a book and discussed the day's events to her maid, Estrella, then also contemplated the two fine men in her life: James Norrington and Will Turner. Meanwhile, a pirate ship, the Black Pearl, which Elizabeth discovers is the same ship she saw eight years earlier, began an attack on the town of Port Royal. At the Governor's mansion, Pintel and Ragetti were chasing Elizabeth until she invoked the right of parley, in which she had to be taken to their captain. She is kidnapped because she possesses Will's gold medallion. Taken aboard the Black Pearl, Elizabeth negotiates with the wily Captain Barbossa to leave Port Royal in exchange for the coin. He agrees but keeps her captive on a technicality after she identifies herself as Elizabeth "Turner", mistakenly believing she was the child of William "Bootstrap Bill" Turner and that her blood can break an ancient Aztec curse the pirates are under.

In the wake of Elizabeth's kidnapping, her childhood friend, Will Turner, joins forces with Jack Sparrow in a gallant attempt to rescue Elizabeth and recapture the Black Pearl. The duo escaped from Commodore Norrington while commandeering the fastest ship in the British fleet, the HMS Interceptor, and recruited a ragtag crew race toward the mysterious Isla de Muerta. Unbeknownst to Elizabeth, a cursed treasure has doomed Barbossa and his crew to live forever as the undead, the moonlight eerily transforming them into living skeletons. The curse they carry can be broken only if the plundered treasure is restored in total and a blood debt repaid. While having dinner with Barbossa, Elizabeth learned about the curse after confronting Barbossa with a knife and saw a skeleton crew on deck. After her terrifying chase around the moonlit deck, she cowered in a corner of the captain's cabin for the rest of the voyage.

Elizabeth and Barbossa during the blood ritual. Upon arriving at Isla de Muerta, Elizabeth reluctantly joined the cursed crew into the treasure-filled caves, where she saw the Chest of Cort's and was forced to take part in a blood ritual. Barbossa attempted to lift the curse by returning the final cursed coin into the chest, with a portion of Elizabeth's blood, believing it to be the blood of a Turner. The ritual failed, however, and Barbossa asked Elizabeth if her father was William Turner, and she told him "No". When refusing to reveal who and where Turner's real child was, Barbossa knocked Elizabeth to the ground. Fortunately for Elizabeth, while Barbossa and his crew were arguing, Will Turner arrived in time to flee the island with her and his medallion. When he reached the island, Will suspected Jack may betray him and knocked him out, so when he rescued Elizabeth, he left Jack behind. She was brought aboard the Interceptor and was shocked to find more pirates, though saw the familiar face of Joshamee Gibbs. But even though they sailed a fair distance, the Black Pearl was in high pursuit. Although the Interceptor tried to outrun the Pearl, both ships engaged in battle. As the ships turned for attack, Elizabeth shouts "Fire all!" to start the battle. Ultimately, Barbossa's crew won the battle, having successfully taking back the medallion and sinking the Interceptor. While the crew had their way with Elizabeth, Will reveals he is Bootstrap Bill's child and demanded that Elizabeth be freed and Jack's crew would not be harmed, or he will shoot himself and fall overboard, foiling Barbossa's plan to break the curse. Barbossa agrees but applies another loophole, keeping Jack's crew imprisoned while making Elizabeth and Jack Sparrow walk the plank near the same island Jack had been left on ten years earlier.

While Will and the crew are thrown in the brig, with Will being taken as Barbossa's prisoner to Isla de Muerta, to be killed to break the curse, Elizabeth and Jack were marooned on a desert island with no hope of escape. However, Elizabeth discovers how Jack escaped before: the island was used as a cache by rum runners and Jack bartered passage. That night Elizabeth taking action for their rescue by burning a cache of smugglers' rum, much to Jack's disappointment. The towering smoke column is spotted by Commodore Norrington's ship, the Dauntless. To rescue Will, Elizabeth convinces Norrington to attack Isla de Muerta by impulsively accepting his previous marriage proposal. The commodore doubts her sincerity, though Elizabeth apparently intends to honor her promise. She says nothing about the curse while Sparrow provides the bearings to Isla de Muerta, setting his own plan into motion.

During the thrilling confrontation with Barbossa's pirates on Isla de Muerta, Elizabeth frees Jack's crew from the Black Pearl's brig, naively believing they will help rescue Will. Abiding by the Pirate's Code that, "any man who falls behind, is left behind," they instead commandeer the Black Pearl and set sail, leaving a disgusted Elizabeth to rescue Will and Sparrow alone. Prior to leaving, Elizabeth told them they were pirates and that they should "hang the Code and hang the rules," saying they were more like "guidelines," which she took from something Barbossa told her days prior. As Norrington's men battle the cursed pirates in the moonlight, Sparrow duels Barbossa inside the treasure cave, while Elizabeth joins Will in his own fight. Looking over, she watched as Barbossa and Jack slashed at each other, nothing more than skeletons in the moonlight. "Whose side is Jack on?" Elizabeth asked, upon seeing that Jack had taken on his old crew's curse. "At the moment?" Will retorted sarcastically. Will and Elizabeth then faced the remaining cursed crewmen. In the end, right when Barbossa pulled out his pistol and aimed straight at Elizabeth, a shot rang out. But it was not Barbossa's pistol that had been fired. Perplexed, Barbossa turned and looked at Jack Sparrow, who stood holding his smoking pistol pointed directly at Barbossa's heart. Jack fatally shoots Barbossa, who boasted about his immortality, until Will opened his left hand, cut in his palm, and two pieces of Aztec gold fell with a clink into the filled chest. From where she stood, Elizabeth smiled before watching Barbossa turn back to Jack, a look of anguish on his face. Having reverted to mortal form as the curse is lifted, Barbossa fell dead. The surviving now-mortal pirates surrender. Will, Elizabeth, and Sparrow are rescued, although Sparrow is later condemned to hang because of the Pearl being gone.

In Port Royal, Elizabeth attends Jack Sparrow's execution. Will, who has been given clemency, approaches Elizabeth and proclaims his love for her before attempting to rescue Sparrow. Will frees Sparrow, but they are quickly captured. Though Commodore Norrington and Governor Swann are reluctant to arrest Will, they were disappointed in his disrupting Sparrow's execution. Will says his place was between Norrington and Jack. Elizabeth intervenes and declares her place alongside Will. Realizing Elizabeth loves Will, Norrington concedes Elizabeth's hand to him. Jack Sparrow, meanwhile, gave his farewell (telling Elizabeth "it would never have worked between us") and falls off the fort and into the bay just as the Black Pearl sails into view. While Jack is hauled aboard, captain of the Pearl once again, Norrington graciously gave both Will and Elizabeth the best of luck and wished them a happy life before saying he'll give Jack Sparrow one day's head start. As Norrington's men leave, Governor Swann inquired about Elizabeth's decision, as Will was a blacksmith. Knowing she made the right decision, as Will was also a pirate, Elizabeth and Will shared their first kiss.

For the next year, Will and Elizabeth's relationship remained strong, to a point of Will training Elizabeth on how to use a sword, and were on the verge of marriage. However, on their wedding day, Port Royal had unexpected guests: Lord Cutler Beckett of the East India Trading Company. Arriving at the altar, Elizabeth sees Beckett and his men with Will shackled in irons. Despite the help from her father, Governor Weatherby Swann, both Elizabeth and Will are charged with execution for aiding Jack Sparrow's escape from his death sentence; with their punishment being also death. Former Commodore James Norrington is also implicated, although he has since resigned his commission and disappeared. Meanwhile, Jack himself has a debt to pay he owes his soul to the legendary Davy Jones. Jack has to escape his debt or end up in an afterlife in service of Jones, otherwise he'll be hunted by the Kraken.

While Elizabeth was in prison, Will was brought to Beckett's office. Will and Governor Swann later visited Elizabeth's cell, where Will revealed that Beckett offered their freedom if Will agrees to search for Jack Sparrow and bring back his compass. Despite Governor Swann's mistrust of the situation and of Beckett, a ruthless East India Trading Company agent, Will leaves to start his search for Jack in Tortuga. Later, while Elizabeth sat in her prison cell, Governor Swann attempts to free her and arranged passage for her back to England. On the way via carriage, Governor Swann was accosted by Beckett's clerk, Mercer, foiling his plan of freeing his daughter. But while Governor Swann was taken into custody, Elizabeth had gone to Cutler Beckett's office, confronting Becket himself at gunpoint, forcing him to validate a Letters of Marque to free Will. Elizabeth fled to find Will Turner, stowing away aboard the Edinburgh Trader, disguising herself as a cabin boy. After the crew found her dress lying around, which caused a worry that there is a spirit bringing an omen of ill-fate, Elizabeth tricks the merchant crew into sailing to Tortuga.

Upon arriving to Tortuga, she jumped ship to find Jack Sparrow, who was with Joshamee Gibbs in a pub recruiting sailors to pay off Jack's debt to Davy Jones, who demanded one hundred souls in exchange for Jack's. Another man applies James Norrington, now a penniless drunk. Blaming Sparrow for his ruined life, Norrington attempts to shoot him, igniting a brawl, but Elizabeth knocks him out. After Norrington was thrown into the pig pen and left alone, Elizabeth formally reunited with him. The two head off to find Jack and Gibbs at the docks. Elizabeth inquired about Will's whereabouts, in which, Jack claims that Will was press-ganged into Davy Jones' crew, insisting he was blameless; Norrington is skeptical, but Elizabeth places her faith in Jack when he tells her she can save Will by finding the Dead Man's Chest, which held the still-beating heart of Davy Jones. Unfortunately, Jack's magic compass seems to fail him, though it may be pointing to something he unknowingly desires more than the Chest. Using his magical compass, she gets a heading. Both Elizabeth and Norrington join aboard the Black Pearl, with Norrington joining as a hired crewman. While sailing to their destination, after Elizabeth revealed what she knew, the party realizes that if Beckett gains the Chest then he will rule the seas. Meanwhile, Will hitches a ride on the Edinburgh Trader, which is destroyed by the Kraken, by which time Jones realises Jack is after the Chest.

On Isla Cruces, Jack, Elizabeth, and Norrington find the Dead Man's Chest. When Will arrives, Elizabeth and Will kiss since they have found each other at last. It was in that moment Elizabeth learns that Jack tricked Will onto the Dutchman. With Will holding Davy Jones' stolen key, a conflict erupts: Will wants to kill Jones by stabbing the heart, freeing his father from Jones' servitude; Jack fears the Kraken will continue hunting him if Jones is dead; Norrington plots to barter back his naval career. As a three-way duel erupts, Jones' crewmen arrive. Elizabeth fought against Jones' crew while pursuing Pintel and Ragetti, who stole the Chest. In the chaos, Jack unlocks the chest, removes the heart, and hides it in the jar of dirt, only for Norrington to secretly remove it and then pretends to sacrifice himself by drawing the Dutchman crew off with the chest, which he gives to them.

Climbing back aboard the Black Pearl, Jack's crew are confronted by the Flying Dutchman but the Pearl is able to outrun it. This leads to an escalating confrontation with the Kraken, summoned by Davy Jones to take down the Pearl. To save himself, Jack escapes in the only remaining longboat, prompting Elizabeth to brand him a coward. But as Elizabeth once predicted, Jack, unable to desert his crew, heroically returns to rescue them, reaffirming her faith in him. During the Kraken's brief retreat, Jack orders all hands to abandon ship. Realizing Jack is what the Kraken was after, Elizabeth distracts him with a passionate kiss while handcuffing him to the mast in order to save Will and other members of Jack's crew. Though she claims she has no regrets, her overwhelming guilt belies her true feelings. It is during this moment that Elizabeth becomes more pirate-like to save herself and the crew. Even Jack acknowledges this when he calls her "pirate" before Elizabeth leaves. She tells the others Jack stayed behind to aid their escape, unaware Will witnessed their encounter. The Kraken returns for its final assault, dragging the Black Pearl to the depths along with its captain, with Elizabeth and the other survivors watching.

While Beckett is given the heart of Davy Jones by Norrington, the grieving members of Jack's crew make their way upriver to Tia Dalma, the flamboyant soothsayer who helped Jack before. As the crew drink a somber toast to their fallen captain, Elizabeth is wracked with guilt over sacrificing Jack to the Kraken. This causes Will to mistakenly believe that Elizabeth loves Jack, and he despondently comforts her, prompting Tia Dalma to ask if they are willing to rescue Jack and the Pearl. When all the crew say "aye", except for Elizabeth who says "yes", Tia Dalma says they will need a captain who knows those waters. To their surprise, the captain is revealed to be the resurrected Captain Barbossa, who asks what has become of "his" ship.