Gruenwald got his start in comics fandom, publishing his own fanzine, Omniverse, which explored the concept of continuity.

Hired initially as an assistant editor in January 1978, Gruenwald was promoted to full editorship by Marvel editor-in-chief Jim Shooter in 1982, putting Gruenwald in charge of The Avengers, Captain America, Iron Man, Thor, Spider Woman, and What If.

He made a deliberate effort to create villains who would be specific to Captain America, as opposed to generic foes who could as easily have been introduced in another comic.

However, he considered his magnum opus to be the mid-1980s 12-issue maxiseries Squadron Supreme, which told the story of an alternate universe where a group of well-intended superheroes decide that they would be best suited to run the planet.

[20] They later divorced, and he married Catherine Schuller on October 12, 1992, in New York after a year's courtship; she was the executor of Gruenwald's famous will.

Gruenwald was a well-known practical joker and, due to his young age, many of his friends and co-workers initially believed the reports of his death to be just another joke.

[21] The Amalgam Comics book The Exciting X-Patrol #1 (June 1997) and the Marvel Comics book Generation X #21 (November 1996) are dedicated to Gruenwald's memory as was Peter Parker: Spider-Man #75 which saw the return of Norman Osborn after his supposed death twenty years earlier.

In the DC Universe, a building in Gotham City was named the Von Gruenwald Tower,[22] and in the novel Captain America: Liberty's Torch written by Tony Isabella and Bob Ingersoll, the lawyer kidnapped to defend the similarly kidnapped Captain America in a mock trial before a militia is named Mark Gruenwald, and is described with the same general physical attributes and personality as the real Gruenwald.