A gang of bandits attacks the population of Río Hondo, shooting left and right; a man decides to act.

A Southern Colonel, his three sons, and a card shark embark on an odyssey through the Southwest carrying a coffin full of stolen money with which the Colonel plans to revive the Confederacy.

William Shatner plays two roles: cowboy Johnny Moon and his ruthless Indian twin brother, Notah. Notah likes peyote and gets the crazy idea that he's the Comanche messiah sent to lead the Comanche nation against the white man but more specifically the dusty desert town of Rio Hondo. Moon, estranged from his brother, decides to stop Notah either by words or by bullets.