On the show, Cheyenne many times took various temporary law enforcement positions. Prior to becoming an actor, Clint Walker was a Deputy Sheriff.

Cheyenne gets his name from the Cheyenne Indians, who killed his parents, but then took him in and raised him.

Clint Walker had a contract dispute with Warner Brothers, which led to him briefly leaving. Under his contract, Walker had to give them fifty percent of his personal appearance fees, and could only record music under the Warner Brothers label. He wanted the amount cut, and to be able to sign with whatever record company he chose. The sides reached an agreement, and Walker eventually returned to work.

This was U.S. television's first hour-long western.

Contrary to popular belief, Clint Walker did not take his shirt off in every episode of the series. For example, in the fifteen shows which constituted the first season of this show, Walker appeared bare-chested in only six of them: episode three, "The Argonauts", episode eight, "The Storm Riders", episode nine, "Rendezvous at Red Rock", episode eleven, "Quicksand", episode twelve, "Fury at Rio Hondo", and episode fourteen, "Johnny Bravo".

Cheyenne started out with a sidekick named Smitty, played by L.Q. Jones. He was dropped after three episodes, and Cheyenne went the rest of the way alone.

Many of the first year's episode were remakes of Warner Brothers western films, so the studio could use footage from those films to save money.

It was the longest-running of the Warner Brothers family of westerns, lasting seven seasons.

Many of the Indian characters on the show were played by white people, which was normal for most western television shows and movies of that era.

The first original television series produced by a major Hollywood film studio, Warner Brothers. (While Walt Disney's Wonderful World of Color (1954) had premiered the year before, it did not consist of programming made exclusively for television).

Contrary to popular belief, Clint Walker did not take his shirt off in every episode. In fact, of the one hundred seven episodes in which Walker appeared, he only was seen bare-chested in twenty-five of them. The breakdown is as follows: in season one, six episodes; in season two, six episodes; in season three, seven episodes; in season four, four episodes; and in season six, two episodes.

For a few seasons, the series became "The Cheyenne Show", which had Cheyenne (1955) rotating weekly with Sugarfoot (1957) and Bronco (1958).

Cheyenne's pistol was seen in an episode of 77 Sunset Strip (1958) (season six, episode five, "5: The Conclusion"). Cal Jasper (Clint Walker) loaned his gun to Stuart Bailey (Efrem Zimbalist, Jr.).