Mystery in Space was a science fiction comic book published by DC Comics from 1951 to 1966, and later in 1980/81 (issues #111-117). It featured artwork by Murphy Anderson, Gil Kane, and many others, stories by John Broome, Gardner Fox, and others. It was an anthology comic for many years, publishing a variety of science fiction stories, and several science-fiction based heroes. It may be best known for publishing the adventures of Adam Strange.

The comic won several awards, including the 1962 Alley Award for Best Book-Length Story ("The Planet That Came to a Standstill!" in #75 by Gardner Fox and Carmine Infantino) and the 1963 Alley Award for Comic Displaying Best Interior Color Work.

In 1980, Fireside Books published the oddly plural Mysteries in Space: The Best of DC Science Fiction Comics (ed.: Michael Uslan), which reprinted 11 stories from the original run (including the aforementioned #75), plus 13 stories from other DC science fiction comics.

A trade paperback by almost the same title, Mystery in Space (Pulp Fiction Library), reprinted some of the same stories, but added other stories from the series. This trade paperback won seventh place for the Comics Buyer's Guide Fan Award for Favorite Reprint Graphic Album for 2000.

DC revived Mystery in Space in September 2006 as an eight-issue miniseries written by Jim Starlin and drawn by Shane Davis. The series featured a new Captain Comet and is described as a "detective story set in the far reaches of the DCU". The first seven issues contain a backup story starring The Weird (from the eponymous 1988 miniseries), with art by Starlin.