Jerry Siegel and Joe Shuster saw their creation, Superman , AKA Kal-El (originally Kal-L), launched in Action Comics #1 in April 1938 (cover-dated June). (Approximate present-day value (In "near mint" condition): $1,380,000 USD.) Siegel and Shuster had tried for years to find a publisher for their Superman character (originally conceived as a newspaper strip) without success. Superman was originally a bald madman created by Siegel and Shuster who used his telepathic abilities to wreak havoc on mankind. He appeared in Siegel and Shuster's book Science Fiction. Siegel then commented, "What if this Superman was a force for good instead of evil?" The writer and artist had worked on several features for National Periodical Publications' other titles (Slam Bradley in Detective Comics, for example) and were asked to contribute a feature for National's newest publication. They submitted Superman for consideration, and after re-pasting the sample newspaper strips they had prepared into comic book page format, National decided to make Superman the cover feature of their new magazine. The dynamic "Man of Tomorrow" was an instant hit, and he permanently changed the medium of comic books and comic strips by formalizing a new fantasy subgenre. Action Comics was soon followed by the Superman comic book series in 1939, along with a wealth of other comics starring numerous costumed superheroes.

As of 2007, Action Comics is still in publication, surpassing a milestone of 850 issues. This makes it the second-highest-number American comic book series, after Dell Comics' Four Color.

Action Comics is the second-longest running DC Comics series after Detective Comics; however, it cannot claim to have had an uninterrupted run, as it went on hiatus for three months twice, once in 1986 (when the regular Superman books were suspended during the publication of John Byrne's The Man of Steel six-issue limited series, and again in 1992 (when the Superman books went on a 3-month hiatus following the "Death of Superman" and "Funeral for a Friend" stories).

In 1988, DC Comics tried unsuccessfully to return the format of the comic to an anthology and publish it on a weekly basis, but it returned to a monthly format less than a year later. (However, the temporarily increased frequency of issues allowed Action to further surpass the older Detective Comics in the number of individual issues published. It originally passed Detective Comics in the 1970s when that series was bi-monthly for a number of years.) Another departure from a strict monthly schedule were the giant-size Supergirl reprint issues of the 1960s and very early 1970s (published as a 13th issue annually).

Originally, Action Comics was an anthology title featuring a number of other stories in addition to the Superman story. Zatara, a magician, was one of the other characters who had their own stories in early issues. (Zatanna, a heroine introduced in the 1960s, is Zatara's daughter.) There was also the hero Tex Thomson, who eventually became Mr. America and later the Americommando. Vigilante also enjoyed a lengthy run in this series. Sometimes stories of a more humorous nature were included, such as those of Hayfoot Henry, a policeman who talked in rhyme. Gradually the size of the issues was decreased as the publisher was reluctant to raise the cover price from the original 10 cents, so there were fewer stories. For a while, Congo Bill and Tommy Tomorrow were the two features in addition to Superman (Congo Bill eventually gained the ability to swap bodies with a gorilla and his strip was renamed Congorilla), but soon after the introduction of Supergirl in issue #252 (May 1959) the non-Superman-related strips were crowded out of Action altogether. Since then, it has generally been an all-Superman comic, though other backup stories such as The Human Target occasionally appear.