Adventure Comics began its nearly 50-year run in 1935 under the title New Comics, which was only the second comic book series published by National Allied Publications, now DC Comics. Originally a humor series, the series, which was subsequently retitled New Adventure Comics with its seventh issue, gradually shifted to a serious adventure series. Issue 32 saw the title again changed to Adventure Comics, which would remain the book's name for the duration of its existence. The series' focus gradually shifted to superhero stories starting with the debut of The Sandman in issue #40. Other superheroes who appeared in the early days of Adventure included Manhunter and Starman.

A pivotal issue of the series was #103, when Superboy, Green Arrow, Johnny Quick and Aquaman moved from More Fun Comics (which was being converted to a humor format) to Adventure. Starman and Sandman's stories were canceled to make room for the new features. Superboy became the star of the book, and would appear on each cover through 1969.

In issue #247 (April 1958), Superboy met the Legion of Super-Heroes, a team of super-powered teens from the future. The group became popular, and would soon take over as the Adventure lead feature through issue #381 (June 1969), in which Supergirl migrated from the backup feature in Action Comics to the starring feature in Adventure.

In 1973, the book's theme changed from superhero adventure to supernatural adventure. The Spectre and Black Orchid were the stars of the book during this era. Before long, though, conventional superheroes returned to the book. The last decade of Adventure starred a variety of characters, and features, including Aquaman, a new Starman, "Dial H for Hero" and the Justice Society of America. The book ended its run as a digest-sized reprint anthology.

DC published an Adventure Comics #1 as part of the company's "Justice Society Returns" storyline in 1999.