Detective Comics was the final publication of the entrepreneur Major Malcolm Wheeler-Nicholson, whose comics company, National Allied Publications, would evolve into DC Comics, one of the world's two largest comic book publishers, though long after its founder had left it. Wheeler-Nicholson's first two titles were the landmark New Fun: The Big Comic Magazine #1 (Feb. 1935), colloquially called New Fun Comics #1 and the first such early comic book to contain all-original content, rather than a mix of newspaper comic strips and comic-strip-style new material. His second effort, New Comics #1, would be retitled twice to become Adventure Comics, another seminal series that ran for decades until issue #503 in 1983.

The third and final title published under his aegis would be Detective Comics, advertised with a cover illustration dated Dec. 1936, but eventually premiering three months late, with a March 1937 cover date. In 1937, however, Wheeler-Nicholson was in debt to printing-plant owner and magazine distributor Harry Donenfeld, who was as well a pulp-magazine publisher and a principal in the magazine distributorship Independent News. Wheeler-Nicholson took Donenfeld on as a partner in order to publish Detective Comics #1 through the newly formed Detective Comics, Inc., with Wheeler-Nicholson and Jack S. Liebowitz, Donenfeld's accountant, listed as owners. Wheeler-Nicholson was forced out a year later.

Originally an anthology comic, in the manner of the times, Detective Comics #1 (March 1937) featured stories in the "hard-boiled detective" genre popular, with such stars as Ching Lung (a Fu Manchu-style "yellow peril" villain), Slam Bradley (created by Jerry Siegel and Joe Shuster before their character Superman saw print two years later), and Speed Saunders, among others. Its first editor, Vin Sullivan, also drew the debut issue's cover.

Batman

Detective Comics #27 (May 1939) featured the first appearance of Batman (as "The Bat-Man"). That superhero would eventually become the star of the title, the cover logo of which is often written as "Detective Comics featuring Batman".

Issue #38 (April 1940) introduced Batman's sidekick Robin (billed as "The Sensational Character Find of 1940" on the cover). Robin's appearance and the subsequent increase in sales of the book soon led to the trend of superheroes and young sidekicks that characterize the era fans and historians call the Golden Age of Comic Books.

In addition to the Batman stories, the comic also had numerous back up strips such as "Martian Manhunter" which was introduced in Detective Comics #225.

In the late 1970s and early 1980s, the magazine adopted the expanded format used by the cancelled Batman Family, adding solo features including "Robin: the Teen Wonder", "Batgirl", "The Human Target" and the anthology called "Tales of Gotham City", which featured the stories of the ordinary people of Gotham City.