John "Hombre" Russell, portrayed by Paul Newman, is a man of patience as he waits for a black stallion to lead its herd to a nearby waterhole. His plan is to trap the horses along with his San Carlos Apache tribesmen, with the intention of selling them to a local stagecoach line. However, Henry Mendez, played by Martin Balsam, informs John that the stagecoach line is on the verge of shutting down due to the encroaching railroad. He encourages John to embrace his familial roots and take charge of a boarding house left to him by his late stepfather.
As John inspects the boarding house, he informs the landlady, Jessie (Diane Cilento), of his decision to trade the property for a herd of horses located in Contention, with plans to head to Bisbee, Arizona. Here, Alex Favor, embodied by Fredric March, arrives with his wife, Audra (Barbara Rush), and they charter one last stagecoach to Bisbee. However, trouble brews when Cicero Grimes, played by Richard Boone, pressures his way onto the passenger list alongside John, Jessie, and the Blakes.
Taking precaution, Henry, the stagecoach driver, opts for a back road to Bisbee, prompted by unease over a suspicious group of men in the vicinity. After discovering John's Apache upbringing, Alex requests him to ride atop the stagecoach with Henry. The journey takes a perilous turn when bandits, led by Cicero, ambush the stagecoach. In the chaos, they abduct Audra and seize a significant amount of money from Alex, who secretly embezzled funds from the San Carlos Apaches. Displaying bravery, John retaliates against the bandits, eliminating two of them and reclaiming the stolen cash.
Retreating back towards town through the rugged mountains, the passengers take refuge at an abandoned mining site. However, they are soon confronted by the bandits again. Cicero proposes a trade: Audra for the money. During the tense standoff, John decisively shoots Cicero. In a heart-wrenching development, a bandit binds Audra and leaves her exposed to the scorching sun. Desperate for assistance, Audra pleads for help, but despite the group's desire to save her, fear grips them—except for Jessie, who musters the courage to act.
John intervenes, instructing Jessie to return the cash to the San Carlos Apaches while he bravely descends the hill with the saddlebags. Upon reaching Audra, he frees her, but complications arise as she attempts to climb back to safety, inadvertently obstructing a clear shot at a bandit from their hideout in the shack. Tension mounts when a wounded Cicero confronts John, only to discover that the saddlebag is devoid of cash. In the ensuing chaos, a fierce exchange of gunfire claims the lives of John, Cicero, and the bandit, sealing their fates amidst a gripping tale of bravery and moral dilemmas.