A woman in a wedding dress, the Bride, lies wounded in a chapel in El Paso, Texas, having been attacked by the Deadly Viper Assassination Squad. She tells their leader, Bill, that she is pregnant with his baby. He shoots her in the head.
Four years later, having survived the attack, the Bride goes to the home of Vernita Green, planning to kill her. Both women were members of the assassination squad, which has since disbanded; Vernita now leads a normal suburban family life. They engage in a knife fight, but are interrupted by the arrival of Vernita’s young daughter, Nikki. The Bride agrees to meet Vernita at night to settle the matter, but when Vernita tries to surprise the Bride with a pistol hidden in a box of cereal, the Bride throws a knife into Vernita’s chest, killing her. Nikki witnesses the killing, and the Bride acknowledges that Nikki may one day seek her own vengeance for her mother’s death.
Four years earlier, police investigate the massacre at the wedding chapel. The sheriff discovers that the Bride is alive but comatose. In the hospital, Deadly Viper Elle Driver prepares to assassinate the Bride via lethal injection, but Bill aborts the mission at the last moment, considering it dishonorable to kill the Bride when she cannot defend herself.
The Bride awakens from her four-year coma and is horrified to find that she is no longer pregnant. She kills a man who tries to rape her and a hospital worker who has been selling her body while she was comatose. She takes the hospital worker’s truck and teaches herself to walk again.
Resolving to kill Bill and all four members of the Deadly Viper Assassination Squad, the Bride picks her first target: O-Ren Ishii, now the leader of the Tokyo Yakuza. O-Ren’s parents were murdered by the Yakuza when she was a child; she took vengeance on the Yakuza boss and replaced him after training as an elite assassin. The Bride travels to Okinawa, Japan, to obtain a sword from legendary swordsmith Hattori Hanzō, who has sworn never to forge a sword again. After learning that her target is Bill, his former student, he relents and crafts his finest sword for her.
At a Tokyo restaurant, the House of Blue Leaves, the Bride defeats O-Ren’s elite squad of fighters, the Crazy 88, and her bodyguard, schoolgirl Gogo Yubari. She and O-Ren duel in the restaurant’s Japanese garden; the Bride gains the upper hand and slices the top of her head off with a sword stroke. She tortures Sofie Fatale, O-Ren’s assistant, for information about Bill, and leaves her alive as a threat. Bill asks Sofie if the Bride knows that her daughter is alive.