The Marvel Universe actually exists within a multiverse consisting of thousands of separate universes, all of which are the creations of Marvel Comics and all of which are, in a sense, "Marvel universes". In this context, "Marvel Universe" is taken to refer to the mainstream Marvel continuity, which is known as Earth-616.

(Note: "Marvel Universe" is also the title of a limited series, produced by Marvel Comics, that featured the Monster Hunters, and is occasionally used as a shortened form of the title of the Official Handbook of the Marvel Universe. "Marvel Universe" should also not be confused with Marvel Action Universe, an animated television series that featured products of Marvel's former animation department, or the one-shot comic of the same name which was released concurrently with the TV series.)

Though the concept of a shared universe was not new or unique to comics in 1961, writer/editor Stan Lee, together with several artists including Jack Kirby and Steve Ditko, created a series of titles where events in one book would have repercussions in another title and serialized stories would show characters' growth and change. Headline characters in one title would make cameo or guest appearances in other books. Eventually many of the leading heroes assembled into a team known as the Avengers . This was not the first time that Marvel's characters had interacted with one another—Namor the Sub-Mariner and the Original Human Torch had been rivals in Marvel's "Golden Age"—but it was the first time that the comic book publisher's characters seemed to share a world. The Marvel Universe was also notable for setting its central titles in New York City (by contrast DC heroes live each in a different fictional city). Care was taken to portray the city and the world as realistically as possible with the presence of superhumans affecting the common citizens in various ways.

Over time, a few Marvel Comics writers lobbied Marvel editors to incorporate the idea of a Multiverse; this plot device allows one to create several fictional universes which normally do not overlap (see below or Multiverse (Marvel Comics) for more information). What happens on Earth in the main Marvel Universe would normally have no effect on what happens on a parallel Earth in another Marvel-created universe. However, storywriters would have the creative ability to write stories in which people from one such universe would visit this alternate universe.

In 1982, Marvel published the mini-series Contest of Champions, in which all of the major heroes in existence at the time were gathered together to deal with one threat. This was Marvel's first miniseries. Each issue contained biographical information on many major costumed characters; these biographies were a precursor to Marvel's series of reference material, The Official Handbook of the Marvel Universe, which followed shortly on the heels of Contest of Champions.