Cheyenne was the first hour-long Western television series and the first hour-long dramatic series with continuing characters to last more than one season. It was also the first series produced by a major Hollywood film studio that did not derive from its established film properties.

James Garner was briefly considered for the lead role of Cheyenne Bodie, but he could not be located in time, so the role went to Clint Walker. Garner instead appeared as a guest star in the pilot episode 'Mountain Fortress'.

Clint Walker went on strike from 1958 to 1959, demanding better terms including increased residuals, a reduction of the 50% cut Warner Bros. took from his personal appearance payments, and freedom to record music outside the studio's own label.

During Walker's strike-induced absence, Warner Bros. introduced a near-identical replacement character named Bronco Layne, played by Ty Hardin, who took over as the quasi-main character until Walker returned in 1959.

Even after returning to the show following the contract dispute, during which he had been barred from seeking other work, Walker was unhappy with the role and told reporters he felt like 'a caged animal.'

Cheyenne was a co-winner of the 1957 Golden Globe Award for Television Achievement and received a 1957 Emmy nomination for Robert Watts for Best Editing of a Film for Television.

The series finished at number 13 in the Nielsen ratings for the 1957–1958 season, before declining to number 18, 17, and 28 in subsequent seasons.

A special episode titled 'A Man Named Ragan', aired at the end of season six, served as the pilot for a spin-off series called The Dakotas, though the two shows are only loosely connected since Cheyenne Bodie never appeared in that episode.

Clint Walker reprised the Cheyenne Bodie character decades later, in the 1991 TV movie The Gambler Returns: The Luck of the Draw and in a 1995 time-travel episode of Kung Fu: The Legend Continues titled 'Gunfighters'.