The first four seasons takes place in the Earth-12041 version of the Marvel Comics multiverse, together with Ultimate Spider-Man (2012), Hulk and the Agents of S.M.A.S.H. (2013) and Hulk: Where Monsters Dwell (2016). But the season five takes place in the Earth-17628, together with Guardians of the Galaxy (2015) and Spider-Man (2017).
Adrian Pasdar who voices Iron Man/Tony Stark on the show, also plays General Glenn Talbot on Agents of S.H.I.E.L.D. (2013).
Fred Tatasciore is the only voice actor to voice a character, in his case Hulk, in both The Avengers: Earth's Mightiest Heroes (2010) and Avengers Assemble (2012). Bumper Robinson was also in both series; as James 'Rhodey' Rhodes/ War Machine in The Avengers: Earth's Mightiest Heroes (2010) and as Falcon on Avengers Assemble (2012).
This series was originally considered as a follow up to The Avengers: Earth's Mightiest Heroes (2010) but was later revealed to take inspiration from the movies. Many of the designs were based off The Avengers (2012), Captain America: The Winter Soldier (2014) and Avengers: Age of Ultron (2015). However, the designs from The Avengers: Earth's Mightiest Heroes (2010) were used for a flashback scene.
The Squadron Supreme, first shown in full in the episode The Dark Avengers (2015) are very similar to members of the Justice League, from DC Comics. Nighthawk is Batman, Hyperion is Superman, Speed Demon is The Flash, Dr Spectrum is Green Lantern (and even has the same voice actor as John Stewart's Green Lantern in Justice League (2001) and Justice League Unlimited (2004), Phil LaMarr), Zarda is Wonder Woman and, when revived, Nuke is Captain Atom.
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