The movie opens with Elise (Angelina Jolie) being followed by French police, working with Scotland Yard under the direction of Inspector John Acheson (Paul Bettany). Acheson has spent years attempting to catch Elise's old lover, Alexander Pearce, who owes nearly £800 million in back taxes. While at a cafe, Elise receives instructions from Pearce: board a train to Venice, pick out a man on the way who resembles Pearce, and trick the police into believing that this decoy is the man himself. Elise follows the instructions, picking Frank (Johnny Depp), an American tourist. She spends much time with him, seeming to start a romance. The police recognize the ruse, but it does fool Reginald Shaw (Steven Berkoff), a gangster from whom Pearce stole $2.3 billion.
Pearce leaves further instructions for Elise to attend a ball. Elise abandons Frank, who is then chased by Shaw's men. Through a mishap Frank is arrested by the police, only to have a corrupt inspector attempt to turn him over to Shaw's men in exchange for the bounty on Pierce's head. During the transaction Elise rescues Frank, leading Shaw's men on an extended chase and eventually escaping. Afterward she leaves Frank at the airport with his passport and a satchel full of money, asking him to go home for his own safety.