Brian Kessler (David Duchovny) is a graduate student in psychology and a journalist, who has written an article about serial killers, which draws interest from a Publisher that offers him a book deal. After the book deal advance is spent, Brian realizes that he needs to start working on finishing his book. His photographer girlfriend Carrie Laughlin (Michelle Forbes) persuades him to move to California, they decide to drive from Pittsburgh to California and visit infamous murder sites along the way. Short on funds, Brian posts a ride-share ad.
Meanwhile, sociopathic parolee Early Grayce (Brad Pitt) has just lost his job. His parole officer (Judson Vaughn) learns of this and comes to the trailer park where Early lives with his young girlfriend Adele Corners (Juliette Lewis). Early refuses the officer's offer of a job as a college janitor, saying he wants to leave the state. The officer informs him that, if he does not keep the appointment, he will be returned to prison. Early decides to go to the job interview; and, when he is on his way out, he is confronted by the landlord over non-payment of rent. Early grows violent and spins out in his car, chasing the man all over the park.
Early spies the ride-share ad at the college and calls Brian, who agrees to meet him the following day. Early sends Adele ahead and, as revealed later, murders the landlord before joining Adele to wait for Brian and Carrie. Carrie's first response to seeing the rough-hewn couple is to suggest Brian turn the car around and leave, but Brian asks her to give the plan a chance, and she reluctantly agrees.
On the road, unknown to his companions, Early murders a man in a gas station bathroom and steals his money. When they arrive at the first hotel, he cuts Adele's hair to match Carrie's. At another hotel, Early invites Brian out to play pool, leaving Adele and Carrie alone together. Adele reveals to Carrie that she is a rape victim and that she views Early as her protector, even though her mother did not approve because Early had just been released from prison. Carrie is alarmed by Brian's growing fascination with Early and nonchalant response to the news that Early has been in prison. She gives him an ultimatum; either they rid themselves of Early and Adele, or she will leave.
At the next gas station, Carrie glimpses a newscast with footage of Early and the announcement he is a suspected murderer. Early kills the gas station attendant and continues the trip with the couple as hostages. They encounter two police officers, whom Early shoots. Early orders Brian to finish off one of the wounded officers, but Brian refuses. They next come to the home of an elderly couple. Early beats the man to death, but Adele allows the woman to flee. As Early rushes to find the woman, Adele confronts him and says she wants nothing more to do with him. Early fatally shoots Adele, strikes Brian on the head, and kidnaps Carrie.
Brian regains consciousness, and the elderly woman gives him the keys to her truck. Brian arrives at an abandoned nuclear testing site and surprises Early, hitting him in the head with a shovel. Brian finds Carrie bloodied and handcuffed to a bed, having been sexually assaulted. Early, who was only stunned, attacks Brian and they struggle until Early is hit over the head by Carrie. When Early continues the attack, Brian shoots him in the abdomen. Early is not mortally wounded, Brian realizes this and shoots him again, killing him.
The film ends with Brian and Carrie in a California beach house. Carrie, who now sports long hair (eschewing the short style that Early had Adele emulate during the trip), tells Brian that a gallery is interested in her art, and he suggests they go out to celebrate. He leaves his tape player on; and Adele's voice is heard, talking about how good Carrie and Brian were to her and Early, and how much their friendship means to her.