Thelma Dickinson and Louise Sawyer are best friends who are bored with their lives in Arkansas and want to take a vacation together to a little fishing cabin, hoping to break the monotony. The trip starts to get interesting quite quickly. When they stop at a roadhouse bar for a drink, Thelma, who is married to a controlling car salesman, dances with a stranger who seems to be flirting with her. She enjoys the attention and goes out into the parking lot to get some fresh air with him.
Harlan tries to kiss her but when she pushes him away he becomes violent, trying to tear off her clothes, and attempts to rape her. Louise appears and threatens Harlan with the gun that they brought with them. Harlan starts to walk away but is angry and turns to shout that he should have raped her , which enrages Louise so much that she shoots him. She hits him in the chest, killing him instantly. Thelma shoves Louise into the car and they drive away, stopping at a motel to talk about how they are going to deal with what has happened.
Louise tells Thelma that nobody will believe Harlan was trying to rape her, because she was seen drinking and dancing with him in the bar before they went outside. They will be charged with murder, and despite Thelma's feelings that they should just go to the police and tell them how everything transpired, she agrees to go on the run with Louise, They decide to flee to Mexico, making a plan up as they go. They pick up a hitchhiker named J.D. on the road; Thelma feels an instant attraction to him and so picking him up is her idea.
Louise contacts her boyfriend, Jimmy, who is a musician in a band and away touring the country most of the time. She asks him to wire her life savings but when she goes to pick the money up she finds Jimmy there with it. They spend the night together and Jimmy proposes, but Louise turns him down.
That night Thelma and J.D. also sleep together. J.D. admits that he too is on the run, having broken parole after serving jail time for theft. Thelma has fallen hard for J.D. and so does not think twice about leaving him in their hotel room whilst she goes to eat breakfast with Louise. When they return to the room, J.D. has gone, and so has Louise's life savings. Thelma feels incredibly guilty and to try to reimburse Louise, holds up a convenience store.
The F.B.I. are chasing Thelma and Louise; a witness at the bar told them about the women's car, Louise's 1966 Ford Thunderbird convertible. In Arkansas, Investigator Hal Slocumb questions Jimmy and also puts a wiretap on the telephone at Thelma and her husband Darryl's house. J.D. is picked up too, and questioned. From talking to Jimmy, Slocumb learns that Louise was raped in Texas some years earlier, and begins to feel some sympathy for her. Slocumb manages to talk to Louise on the phone and is gentle, understanding and sympathetic but is unsuccessful in his attempts to get her to surrender herself.
Thelma tells Louise that if she wants to go home, she will completely understand. She has Jimmy, who really loves her. Thelma does not want to return to Darryl; Louise vows to continue together. They are pulled over for speeding by a state trooper in New Mexico. Thelma realizes he will realize that they are wanted by authorities fairly quickly and so she points her gun at him whilst Louise takes his gun and ammunition, before locking him in the trunk of his police cruiser. Their escape attempt continues.
One hundred yards from the edge of the Grand Canyon, Thelma and Louise are finally apprehended. Hal Slocumb arrives in time to see that they have been cornered but is not permitted to speak with them or try to convince them to surrender themselves. The women cannot stand the prospect of spending the rest of their lives in jail and when Thelma proposes that they "keep going", Louise agrees. Louise puts her foot on the gas pedal and they drive over the side of the Grand Canyon.
