Down-on-his-luck country singer Mac Sledge (Robert Duvall) has nowhere to turn when he wakes up in a motel, short on cash. So he takes a job from Rosa Lee (Tess Harper), the kindly widow who runs the place. Mac begins to fall for Rosa, who helps him confront his drinking, and also finds an unexpected bond with Rosa's young son (Allan Hubbard). When the opportunity for a career comeback surfaces, Mac must choose between his new life and the life he let slip through his hands.

In a Manhattan cafe, word processor Paul Hackett (Griffin Dunne) meets and talks literature with Marcy (Rosanna Arquette). Later that night, Paul takes a cab to Marcy's downtown apartment. His $20 bill flying out the window during the ride portends the unexpected night he has. He cannot pay for the ride and finds himself in a series of awkward, surreal and life-threatening situations with a colorful cast of characters. He spends the rest of the night trying to return uptown.

Infamous and unpredictable, Jesse James (Brad Pitt), nicknamed the fastest gun in the west, plans his next big heist while he launches pre-emptive strikes against those looking to collect the reward the law has placed on his head. Jesse's newest recruits, Robert (Casey Affleck) and Charley Ford (Sam Rockwell), grow increasingly jealous of the outlaw. When they sense an opportunity to kill Jesse, they gun him down, but their actions backfire when Jesse's fame is elevated to near mythical status.

A comic-book nerd and Elvis fanatic Clarence (Christian Slater) and a prostitute named Alabama (Patricia Arquette) fall in love. Clarence breaks the news to her pimp and ends up killing him. He grabs a suitcase of cocaine on his way out thinking it is Alabama's clothing. The two hit the road for California hoping to sell the cocaine, but the mob is soon after them.