Walker was a strapping young man of 1/4 Cherokee descent; he stood 6' 6" and reportedly had a 48" chest. He left school to join the United States Merchant Marine at the tail end of World War II then worked at odd jobs in California and Las Vegas. In Los Angeles, a friend in the film business helped get him a few bit parts that brought him to the attention of Warner Bros. who were in the process of developing a western style television series. Walker's good looks and physique landed him an audition and he won the lead role. Billed as "Clint" Walker, he was cast as "Cheyenne Bodie," a cowboy hero set in the post American Civil War era.

Although the series regularly capitalized on Walker's rugged frame with frequent bare-chested scenes, it was well written and acted and proved hugely popular. After eight seasons on the ABC television network, Walker went on to roles in several big screen films including The Night of the Grizzly in 1966 and the following year in the very successful war drama, The Dirty Dozen. During the 1970s he returned to television, starring in a number of made-for-TV western films as well as a short-lived series in 1974 called "Kodiak." Approaching the age of sixty, during the ensuing two decades Walker appeared infrequently in minor roles but still maintained a loyal following from his Cheyenne days and is a popular guest star at Western film festivals and the like.

For his contribution to the television industry, Clint Walker has a star on the Hollywood Walk of Fame at 1501 Vine Street. In 2004, he was inducted into the Western Performers Hall of Fame at the National Cowboy & Western Heritage Museum in Oklahoma City, Oklahoma.