This series was based on an ABC western television series broadcast between 1957 and 1960 which, in its turn, was based on a 1950 Warner Bros. feature film. Wayde Preston starred in Colt .45 as Christopher Colt, an undercover government agent who concealed his identity by posing as a traveling pistol salesman. The comic book series' regular features included one-page text stories with western themes and four-page stories about characters such as Fresno, a karate-chopping Japanese-American cowboy, and his kid buddy Snubby. Issues sometimes included one-page Chris Colt stories or illustrated text articles on western life and lore.
The 3 Colt .45 issues of Four Color (Dell, 1942 series) (#924, 1004, 1058) were counted by Dell as the first 3 issues of this series.