Will Lockhart delivers supplies from Laramie to Coronado, an isolated western town. He immediately ends up tangling with the Waggomans, influential owners of the massive Barb Ranch. Lockhart is quietly searching for information about someone who sold repeating rifles to the Apaches; his brother, a green Army lieutenant, was one of many soldiers killed in an Apache attack on a far reach of the Barb Ranch. Patriarch Alec Waggoman is haunted by dreams of a stranger who intends to kill his adult son, Dave. He is also gradually losing his eyesight and cannot count on the immature and vicious Dave. Lockhart is told by Barbara Waggoman, Alec's niece, that he can collect salt for free and haul it away for freight but Dave Waggoman accuses him of stealing, shoots six of Lockhart's mules and burns his three wagons. Lockhart returns to town, engaging first Dave and then ranch foreman Vic Hansbro in a fistfight. Alec shows up and offers Lockhart restitution for his lost property. Sheriff Tom Quigby suggests that Lockhart then leave town to avoid trouble. Lockhart continues searching for the gun runner. Local drunk Chris Boldt tells him that he may know something, but is killed soon after being seen with Lockhart, leading Sheriff Quigby to briefly arrest Lockhart. Vic considers himself a second son to Alec and is engaged to marry Barbara. Alec depends on and respects Vic, but holds him responsible for the damage Dave caused to Lockhart's property and threatens to take it out of Vic's pay. Dave starts a gunfight and is shot in the hand by Lockhart. Lockhart is overpowered, and Dave shoots him through the hand with Lockhart's own gun. Afterwards, Vic rides after Dave and catches him trying to contact the Apaches to deliver 200 repeating rifles for which the Apaches have paid Vic and Dave in advance. Vic is forced to shoot and kill Dave in self-defense, and then lets Alec believe that Lockhart was responsible. Lockhart takes refuge with a rival rancher, Kate Canady, who wishes she and Waggoman, her long-ago fiancé before he married Dave's future mother, could declare a truce. Alec goes over some old bills and finds a bill for wire fence that is very overpriced. He suspects that it conceals a rifle purchase and sets out to discover for himself if Dave was both stealing from him and selling rifles to the Apaches. Vic is unable to talk him out of it, so just before they reach the wagon, the two scuffle and Alec is accidentally pushed off his horse and down a hill. Assuming the old man is dead, Vic rides away. Lockhart finds Alec alive and takes him to Kate to tend to his wounds. When he regains consciousness, Alec is able to tell Lockhart about Dave and Vic and the rifles. Lockhart finds Vic using a smoke signal to call for the Apaches to come for their rifles. Lockhart forces Vic to help him push the wagon off the hilltop and destroy the rifles, then finds he is unable to gun Vic down in cold blood. Vic rides away, but is intercepted and killed by the Apaches. Alec and Kate plan to get married. Barbara intends to leave Coronado and head back east. As Lockhart leaves town, he tells Barbara she will be passing through Laramie on the way and to ask anyone where to find Captain Lockhart, confirming that he is an officer in the U.S. Cavalry.
Producer Aaron Rosenberg says that the reason Stewart and Mann never worked together again after The Man From Laramie was a disagreement over the quality of Night Passage, which according to Mann was "trash". Mann quit the movie, feeling that Stewart was only making the film so he could play his accordion, something that enraged Stewart so much that the two didn't speak again.