A classic action-filled John Wayne western is set into motion with a spectacular robbery of a Union pay train by Confederate guerrillas. The trains colonel (Wayne) jails the enemy leaders (Jorge Rivero, Chris Mitchum) but the three men later become friends when the war ends. Together they seek the Union traitors responsible for a string of Confederate train robberies, a mission that culminates in a rousing shoot-'em-up finale.

Rio Lobo was the fifth collaboration over a 22-year period between John Wayne and the legendary director Howard Hawks.