Best friends Thelma Dickinson (Geena Davis) and Louise Sawyer (Susan Sarandon) set out for a weekend vacation at a fishing cabin in the mountains to take a break from their dreary lives in Arkansas. Thelma, a ditzy housewife, is married to a disrespectful and controlling carpet salesman, Darryl (Christopher McDonald), while sharp-tongued Louise works as a waitress in a diner and is on–off dating an easygoing musician, Jimmy (Michael Madsen), who spends most of his time on the road.
On the way, they stop for a drink at a roadhouse bar, where Thelma meets and dances with a flirtatious stranger, Harlan (Timothy Carhart). When he takes her outside to the parking lot to get some fresh air, he starts kissing her and taking her clothes off without her consent. Thelma resists, but Harlan becomes violent and then attempts to rape her. Louise finds them and threatens to shoot Harlan with the gun that Thelma brought with her. Harlan stops, but, as the women walk away, he yells that he should have raped her, telling them “I should have gone ahead and fucked her”, before insulting Louise when she turns around. In a fit of rage, Louise responds by shooting Harlan in the chest, killing him instantly. A horrified Thelma ushers Louise to the car and the pair flee the scene.
At a motel, they discuss how to handle the situation. Thelma wants to go to the police, but Louise fears that no one will believe Thelma’s claim of attempted rape since Thelma was drinking and dancing with Harlan, and they will be subsequently charged for murder. They decide to go on the run, but Louise insists that they travel from Oklahoma to Mexico without going through Texas. Something happened to Louise in Texas several years earlier, and Thelma suspects it was something similar to what had happened with Harlan but Louise vehemently says she will not talk about it. Heading west, the women come across an attractive young drifter, J.D. (Brad Pitt), who Thelma quickly falls for, and Thelma convinces Louise to let him hitch a ride with them. Louise contacts Jimmy and asks him to wire transfer her life savings to her. When she goes to pick up the money, she finds that Jimmy has come to deliver the money in person, and the two spend the night together. Jimmy proposes to Louise, but she refuses. Meanwhile, Thelma invites J.D. to her room, and they sleep together. She then learns he is a thief who has broken parole.
The following morning, Thelma leaves J.D. in her motel room to meet Louise downstairs for breakfast, and, when they return, they discover J.D. has stolen Louise’s life savings and fled. Louise is distraught, so a guilty Thelma takes charge and later robs a nearby convenience store using tactics she learned from listening to J.D. Meanwhile, the FBI is getting closer to catching the fugitives after witnesses at the bar saw Louise’s 1966 Ford Thunderbird convertible speeding out of the parking lot the night of the shooting. Their whereabouts are also questioned by the owner of the fishing cabin after the women failed to arrive for the weekend. Arkansas State Police Investigator Hal Slocumb (Harvey Keitel), leading the investigation, questions both J.D., who was caught, and Jimmy and taps into the phone line at Darryl’s house. He discovers that Louise had been raped years earlier in Texas, so he sympathizes with her situation and understands why they didn’t report Harlan’s murder to the authorities. During a couple of brief phone conversations with Louise, he expresses his sympathy but is unsuccessful in his attempts to persuade her to surrender.
Thelma tells Louise she understands if she wants to go back home, knowing she has Jimmy waiting for her, but explains she cannot go back to Darryl. Louise promises they will keep going together. While back on the road, Thelma reflects on what Harlan had done with her and tries to ask Louise if what happened with her also happened to Louise in Texas. Louise angrily says she is not talking about it and tells Thelma to never bring it up again. Later, they are pulled over by a New Mexico state trooper for speeding. Knowing he will soon discover they are wanted for murder and armed robbery, Thelma holds him at gunpoint and locks him in the trunk of his police car, while Louise takes his gun and ammunition. They drive away from the scene and spend the next few nights heading further west. On the road, they encounter a foul-mouthed truck driver who repeatedly makes obscene gestures at them. They pull over and demand an apology from him; when he refuses, they fire at the fuel tanker he was driving, causing it to explode. The women leave him stranded in the desert with the tanker’s wreckage.
Thelma and Louise are finally cornered by the authorities only one hundred yards from the edge of the Grand Canyon. Hal arrives on the scene, but he is refused the chance to make one last attempt to talk the women into surrendering. Rather than be captured and spend the rest of their lives in jail, Thelma proposes that they “keep going”. Louise asks Thelma if she is certain, and Thelma says yes. They kiss, Louise steps on the gas, and they accelerate over the cliff as Hal desperately pursues them on foot.