Double-crossed and left without water in the desert, Cable Hogue is saved when he finds a spring. It is in just the right spot for a much needed rest stop on the local stagecoach line, and Hogue uses this to his advantage. He builds a house and makes money off the stagecoach passengers. Hildy, a prostitute from the nearest town, moves in with him. Hogue has everything going his way until the advent of the automobile ends the era of the stagecoach.

One evening, Hammer gives a ride to Christina, an attractive hitchhiker on a lonely country road, who has escaped from the nearby lunatic asylum. Thugs waylay them and force his car to crash. When Hammer returns to semi-consciousness, he hears Christina being tortured until she dies. Hammer, both for vengeance and in hopes that "something big" is behind it all, decides to pursue the case.

When petty criminal Luke Jackson is sentenced to two years in a Florida prison farm, he doesn't play by the rules of either the sadistic warden or the yard's resident heavy, Dragline, who ends up admiring the new guy's unbreakable will. Luke's bravado, even in the face of repeated stints in the prison's dreaded solitary confinement cell, "the box," make him a rebel hero to his fellow convicts and a thorn in the side of the prison officers.

As the west rapidly becomes civilized, a pair of outlaws in 1890s Wyoming find themselves pursued by a posse and decide to flee to South America in hopes of evading the law.

Questions arise when Senator Stoddard attends the funeral of a local man named Tom Doniphon in a small Western town. Flashing back, we learn Doniphon saved Stoddard, then a lawyer, when he was roughed up by a crew of outlaws terrorizing the town, led by Liberty Valance. As the territory's safety hung in the balance, Doniphon and Stoddard, two of the only people standing up to him, proved to be very important, but different, foes to Valance.