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.

Jim Vesser and his team of railroading men try to build a rail line through a mountain pass, while a group of less scrupulous construction workers sabotages the entire operation in the hopes that they can get their tracks laid first and get the money from the railroad.

Holmes and Watson board a passenger train bound from London to Edinburgh, to guard the Star of Rhodesia, an enormous diamond worth a fortune belonging to an elderly woman of wealth; but within the first hour of the trip, the woman's son is murdered and the diamond stolen and any of the passengers in their car could be the killer thief.