Four of the Reno Brothers are corrupt robbers and killers while a fifth, Clint (Denver Pyle) is a respected Indiana farmer. A sister, Laura (Mala Powers), who has inherited the family home, serves as a housekeeper and cook to the brothers. Some of them served in the Civil War, which has given them a hardened attitude toward violence. One brother is killed when they go after a bank in a nearby town, leading them to draw the conclusion that someone that they know is an informant, as the men of the town appeared to have been waiting for them. They soon learn that it was Murphy, a local bartender, whom they then murder by knocking him out, and tying him up in his barn, which they then set ablaze. The bartender was in fact an agent employed by the Peterson (in real life, Pinkerton) Detective Agency sent to investigate and provide information about the Reno Brothers' crimes.

His replacement is Scott's character, James Barlow, a former secret agent for the Confederacy, who determines to join the gang by posing as a train robber, a ploy which is aided by his being allowed to pull off a staged train robbery (with the full cooperation of the train crew) in the area. (He also begins courting the sister.) Grudgingly accepted by the brothers (led by Tucker's character, Frank Reno), he soon learns that they have corrupted local officials, including a judge (played by veteran character actor Edgar Buchanan), allowing them to operate in that part of the state with near-impunity. The brothers plan a train robbery with Barlow, but this proves to be a setup in which they are captured following a shootout and taken to an area jail outside the jurisdiction of the corrupted officials. (In the shootout, Barlow's fellow Peterson agent, Monk Claxton, is killed.) Townspeople are incited to mob violence and break into the jail and lynch the brothers before they can be brought to trial despite Barlow's best efforts to stop this. (Apparently the sister accepts his efforts as genuine; in the film's final scene she is still with Barlow.)