In 1880, a motley group of strangers boards the east-bound stagecoach from Tonto, Arizona Territory to Lordsburg, New Mexico Territory. Among them are Dallas (Claire Trevor), a prostitute who is being driven out of town by the members of the "Law and Order League"; an alcoholic doctor, Doc Boone (Thomas Mitchell); Lucy Mallory (Louise Platt), who is traveling to see her cavalry officer husband; and whiskey salesman Samuel Peacock (Donald Meek).
When the stage driver, Buck (Andy Devine), looks for his normal shotgun guard, he is told by Marshal Curly Wilcox (George Bancroft) that he has gone out to look for a fugitive, the Ringo Kid (John Wayne). Buck tells Marshal Wilcox that Luke Plummer (Tom Tyler) is in Lordsburg. Knowing that the Kid has vowed to avenge the deaths of his father and brother at Plummer's hands, the marshal decides to ride along.
As they start to pull out, U.S. cavalry Lieutenant Blanchard (Tim Holt) informs them that Geronimo and his Apaches are on the warpath. His small troop will provide an escort until they get to Dry Fork. Gambler and Southern gentleman Hatfield (John Carradine) joins them. At the edge of town, the stage is flagged down by banker Henry Gatewood, (Berton Churchill), who is sneaking away with $50,000 he embezzled from his bank.
Along the way, they come across the Ringo Kid, whose horse had gone lame and left him afoot. Even though they are friends, Curly has no choice but to take Ringo into custody. As the trip progresses, Ringo takes a strong liking to Dallas.
When they reach Dry Fork, they are informed that the expected cavalry detachment has gone to Apache Wells. Buck wants to turn back, but Curly demands that they vote on it. With only Buck and Peacock objecting, they proceed to Apache Wells. There, Mrs. Mallory faints when she hears that her husband had been wounded in battle. She begins to go into labor. Doc Boone is called upon to help her. Eventually, Dallas emerges holding a healthy baby. Later that night, Ringo asks Dallas to marry him. She does not give him an immediate answer, afraid to reveal her checkered past, but the next morning, she agrees if he promises to give up his plan to take on the Plummers. Encouraged by Dallas, Ringo makes a break for it, but turns back when he sees signs of Indians.
When they reach Lee's Ferry, they find the station and the ferry burned down and the people either dead or having fled. They tie large logs to each side of the stagecoach and float it across the river. Just when they think that they are in the clear, they are chased by Apaches. Curly releases the Kid from his handcuffs to help fight them off. During a long chase, when things look bleak, Hatfield is about to use his last bullet to save Mrs. Mallory from being taken alive when he is fatally wounded. Just then, the 6th U.S. cavalry charges to the rescue.
When the passengers finally arrive in Lordsburg, Gatewood is arrested by the local sheriff, and Lucy is told that her husband's wound is not serious. Dallas begs Ringo not to go up against the Plummers, but he is determined to settle matters. Curly grants him leave and his gun. In the ensuing shootout, the Kid dispatches Luke and his two brothers. He returns to Wilcox, expecting to go back to jail. He asks the lawman to take Dallas to his ranch. However, when Ringo gets on a wagon to say goodbye to her, Curly invites her aboard to ride a ways out of town with Ringo. She climbs up with Ringo, and Curly and Doc laugh and start the horses moving, letting him "escape" with Dallas.