On September 9, 1991, FBI Special Agent Sean Archer survives an assassination attempt by freelance terrorist and homicidal sociopath Castor Troy, but the bullet penetrates Archer’s chest and strikes his son Michael, killing the boy.

Six years later, Archer’s vendetta against Troy culminates in his team’s ambush of Troy and his younger brother and accomplice Pollux at the Los Angeles International Airport. Troy goads Archer with knowledge of a bomb located somewhere in the city set to go off in a few days, but he is knocked into a coma before Archer can learn more. Pollux, in custody, affirms the bomb is real, but does not know its location. At the suggestion of his partner Tito Biondi and Special Ops specialist Dr. Hollis Miller, Archer secretly undergoes a highly experimental face transplant procedure by Dr. Malcolm Walsh to take on Troy’s face, voice, and appearance. Archer is taken to the same high-security prison where Pollux is being held, and slowly convinces Pollux that he is Troy, gaining information on the bomb’s location. Meanwhile, Troy unexpectedly awakens from his coma and discovers his face missing. He calls his gang, and they force Dr. Walsh to transplant Archer’s face onto him. Troy then kills Dr. Walsh, Biondi, and Miller, the only three who realized of the transplant.

At the prison, Archer prepares to tell Biondi of the location but is surprised when Troy appears instead, with Archer’s face. Troy goads Archer that no one knows of the transplant, and that he will take over Archer’s life. Pollux is freed when he willingly tells Troy-as-Archer of the bomb’s location, and Troy disarms the bomb in a dramatic fashion. Troy-as-Archer earns admiration from the FBI office and becomes close to Archer’s wife Eve and daughter Jamie, whom Archer had been neglecting while chasing down Troy.

Meanwhile, Archer-as-Troy escapes after staging a riot and retreats to Troy’s headquarters posing as Troy. There, he meets Sasha, the sister of Troy’s primary drug kingpin, and her son Adam, who reminds Archer of Michael. Archer discovers that Adam is Troy’s son. Troy learns of Archer’s escape and hastily assembles a team to raid his headquarters. The raid quickly turns into a bloodbath, killing numerous FBI agents and several members of Troy’s gang, including Pollux. During this Archer, Sasha, and Adam are able to escape. Archer’s supervisor, Director Victor Lazarro, blames Troy-as-Archer for the numerous slayings. Troy, furious over Pollux’s death, kills Lazarro, making it look like a heart attack. Troy-as-Archer is promoted to acting director as plans are made for Lazarro’s funeral. Archer finds safety for Sasha and Adam. He then approaches Eve, and convinces her to test Troy-as-Archer’s blood to prove his identity. Convinced of her husband’s identity, Eve tells Archer that Troy will be vulnerable at Lazarro’s funeral.

At the ceremony, Archer finds that Troy has anticipated his actions and takes Eve hostage. Sasha arrives, and a gunfight ensues; Sasha manages to save Eve after taking a bullet. Archer promises a dying Sasha to take care of Adam and raise him away from criminal life. Troy flees the church with Archer pursuing him. Before killing two more federal agents, Troy briefly takes Jamie hostage, but she escapes by stabbing him with a butterfly knife that Troy had given her for self-defense. A speedboat chase ensues in which Archer forces Troy to shore by collision, then bests Troy in a melee fight. Troy mutilates his own/Archer’s face to taunt and distract him, but Archer instead gains the upper hand and impales Troy with a spear gun, killing him. Backup agents arrive and address Archer by name, having been convinced by Eve of Archer’s true identity.

After the face transplant surgery is reversed, Archer returns home, adopting Adam into his family and keeping his promise to Sasha.