Mystery in Space is the name of two science fiction American comic book series published by DC Comics, and of a standalone Vertigo anthology released in 2012. The first series ran for 110 issues from 1951 to 1966, with a further seven issues continuing the numbering during an early 1980s revival of the title. An eight-issue limited series began in 2006.

An American comic book is a thin periodical originating in the United States, on average 32 pages, containing comics. While the form originated in 1933, American comic books first gained popularity after the 1938 publication of Action Comics, which included the debut of the superhero Superman. This was followed by a superhero boom that lasted until the end of World War II. After the war, while superheroes were marginalized, the comic book industry rapidly expanded and genres such as horror, crime, science fiction and romance became popular. The 1950s saw a gradual decline, due to a shift away from print media in the wake of television and the impact of the Comics Code Authority. The late 1950s and the 1960s saw a superhero revival and superheroes remained the dominant character archetype throughout the late 20th century into the 21st century.