The focus of the book was on stories about American soldiers (or, G.I.s). Initially, the stories involved Cold War adventures with strong Anti-communist themes, but over time the focus shifted to tales from World War II, and most of the stories from the mid 1950's on were set during this period. As with other media, the World War II setting was sometimes used to discuss themes pertinent to contemporary conflicts such as the Vietnam War.
When DC acquired the rights to the Quality Comics characters and titles, G.I. Combat was one of very few titles that they continued publishing, along with Blackhawk, another war title.
Many notable writers and artists worked on G.I. Combat during its run, including Joe Kubert and Neal Adams.
Each issue of G.I. Combat was a compilation book (composed of several short comic stories), a format that continued throughout its run. There were several popular recurring features, including most notably The Haunted Tank, which was featured in G.I. Combat from 1961 to 1987. Other recurring features included The Bravos of Vietnam (about US Marines in the Vietnam War) and late in its run, a return to Cold War themes with a short-lived recurring feature about 1980's mercenaries.
The title continued uninterrupted for the next 30 years. During the 1970's, G.I. Combat was a 'giant' book, with 148 pages of content. By the 1980's, war comics grew less marketable and comic companies began dropping these titles. DC's Sgt. Rock, The Unknown Soldier, and Weird War Tales as well as Marvel Comics' Sgt. Fury and His Howling Commandos were all discontinued in the 1980's.