Louise invites Thelma, an unhappy and emotionally abused housewife, to go on a road trip to a co-worker's lake house to go fishing. Thelma's obnoxious husband forbids her to go, but fed up, she goes anyway. Along the way, the two stop at a bar. Thelma has an innocent flirtation with a man, but things get out of hand when he attempts to rape her in the parking lot. Louise intervenes with a gun in hand, and he backs off. As she and Thelma are leaving, the guy becomes verbally abusive and insulting. An enraged Louise, a former rape victim, shoots and kills him, even though she could have walked away.
Thelma is horrified but will not abandon her friend, and the two take off in Louise's car. From witnesses, the police piece together information about who may have been involved. On the run and out of money, the girls stop at a gas station. Unknown to Louise, Thelma goes in and robs it, making her a full-blown criminal. While heading for Mexico, the two commit a string of robberies, blow up a redneck trucker's semi, and imprison a cop in the trunk of his patrol car. The police are in hot pursuit, but a sympathetic detective suspects that the parking lot killing may have been provoked. He wants to get to the girls before they are seriously hurt.