Based on Lego Marvel Super Heroes: The Video Game, with the same characters in the film.
- Tony Stark/Iron Man (Played by - Robert Downey, Jr.)
- Steve Rogers/Captain America (Played by - Chris Evans)
- Bruce Banner/Hulk (Played by - Mark Ruffalo/Lou Ferrigno)
- Thor (Played by - Chris Hemsworth)
- Natasha Romanoff/Black Widow (Played by - Scarlett Johansson)
- Clint Barton/Hawkeye (Played by - Jeremy Renner)
- Peter Parker/Spider-Man (Played by - Tobey Maguire)
- Fantastic Four:
- Reed Richards/Mr. Fantastic (Played by - Ioan Gruffudd)
- Susan Storm-Richards/Invisible Woman (Played by - Jessica Alba)
- Johnny Storm/Human Torch (Played by - Chris Pine)
- Benjamin Grimm/Thing (Played by - Michael Chiklis)
- James Howlett Logan/Wolverine (Played by - Hugh Jackman)
- Scott Summers/Cyclops (Played by - James Marsden)
- Jean Grey (Played by - Famke Janssen)
- Bobby Drakes/Iceman (Played by - Shawn Ashmore)
- Hank McCoy/Beast (Played by - Kelsey Grammer)
- Ororo Munroe/Storm (Played by - Halle Barry)
- Charles Xavier/Professor X (Played by - Patrick Stewart)
- Warren Worthington III/Angel (Played by - Ben Foster)
- Piotr Rasputin/Colossus (Played by - Daniel Cudmore)
- Emma Frost (Played by - January Jones)
- Nick Fury (Played by - Samuel L. Jackson)
- Maria Hill (Played by - Cobie Smulders)
- Phil Coulson (Played by - Clark Gregg)
- Silver Surfer (Played by - Doug Jones/Laurence Fishbourne)
- Loki (Played by - Tom Hiddleston)
- Victor Von Doom/Doctor Doom (Played by - Julian McMahon)
- Brotherhood of Mutants:
- Erik Lehnsherr/Magneto (Played by - Ian McKellan)
- Raven Darkholme/Mystique (Played by - Rebecca Romijn)
- Cain Marko/Juggernaut (Played by - Vinnie Jones)
- Jason Wyngarde/Mastermind (Played by - Sam Neil)
- John Allerdyce/Pyro (Played by - Aaron Standford)
- Victor Creed/Sabretooth (Played by - Liev Schreiber)
- Norman Osborn/Green Goblin (Played by - William Dafoe)
- Otto Octavius/Doctor Octopus (Played by - Alfred Molina)
- Eddie Brock/Venom (Played by - Topher Grace)
- Flint Marko/Sandman (Played by - Thomas Hayden Church)
- Mandarin (Played by - Ben Kingsley)
- Aldrich Killian (Played by - Guy Pearce)
- Eric Savin (Played by - James Badge Dale)
- Johann Schmidt/Red Skull (Played by - Hugo Weaving)
- Emil Blonsky/Abombination (Played by - Tim Roth)
- Ivan Vanko/Whiplash (Played by - Mickey Rourke)
- Samuel Sterns/Leader (Played by - Tim Blake Nelson)
- M.O.D.O.K. (Played by -Andy Serkis)
- J. Jonah Jameson (Played by - J.K. Simmons)
- Odin (Played by - Anthony Hopkins)
- Frigga (Played by - Rene Russo)
- Heimdall (Played by - Idris Elba)
- Lady Sif (Played by - Jaimie Alexander)
- Warriors Three:
- Fandral (Played by - Zachary Levi)
- Volstagg (Played by - Ray Stevenson)
- Hogun (Played by - Tadanobu Asano)
The film begins as the Silver Surfer is being pursued by S.H.I.E.L.D. and Iron Man, and is knocked out of the sky by Doctor Doom with his surfboard shattering into several 'Cosmic Shards' that fall onto the Earth. With these shards containing immense power, Doom forges an alliance with Loki and gets together a band of villains to make the powerful "Doom Ray of Doom". However, S.H.I.E.L.D. director Nick Fury calls upon the superheroes of the Marvel Universe to retrieve the shards before they can be captured by Doom and his army.
Sandman and Abomination hold the entire Grand Central Station hostage in search of a Cosmic Shard, and it draws the attention of Iron Man and Hulk, who are later aided by Spider-Man in defeating Sandman and thus securing the Cosmic Shard. Fury then tasks Captain America and Mister Fantastic in finding more shards, and the two head to the Baxter Building, which has fallen under the control of Doctor Octopus. Spider-Man returns to aid the two and they defeat Doctor Octopus, but the Cosmic Shard is stolen by the Green Goblin, who takes it with him to Oscorp Tower. Fury tasks Black Widow and Hawkeye with finding the Cosmic Shard while Spider-Man heads to Oscorp in pursuit of the Goblin, and the three are forced to face Venom inside Oscorp's underground lab while the Goblin once again escapes.
Wolverine works with Iron Man and the Hulk to secure the Raft, a maximum-security prison being raided by escaped prisoners, including Abomination and Sabretooth, both of whom the heroes have to take down. Magneto is revealed to be a mastermind behind the mass breakout and quickly makes his escape from the facility with the help of Mystique. After Magneto uses his powers to destroy Iron Man's armor, Stark goes with Captain America to Stark Tower to retrieve a new suit. Mandarin and Aldrich Killian attack the tower, and Stark intitiates "House Party Protocol", using his suits to defeat the two villains. Elsewhere, Black Widow, Hawkeye and Human Torch are sent by S.H.I.E.L.D. to the Empire State Building, where they infiltrate an undergound HYDRA base and defeat the Red Skull with the help of Captain America.
Captain America and the Human Torch meet with Wolverine and Thor, who takes them to Asgard to find Loki. Upon arrival at the Bifrost Bridge, they find that Loki has allied himself with the Frost Giants, and they fight their way to Loki's domain, where Loki enhances his powers with the Tesseract. Loki unleashes the Destroyer armor on the heroes, but they disable the Destroyer while Loki escapes. While the others argue about what to do with the Tesseract, Wolverine uses the distraction to steal it and take it to Professor X at the X-Mansion. The mansion is attacked, and Jean Grey, Cyclops, Storm, Iceman and Beast work together to rescue trapped students and defeat Juggernaut.
At this time, Fury decides to initiate Operation: Latveria to go and stop Doctor Doom. Fury and the Fantastic Four travel to Castle Doom to find him, but instead battle the Green Goblin. Iron Man, Thor and Spider-Man head to a submarine where they defeat MODOK and his forces, being aided by Jean Grey in an attempt to find Doom underwater following the submarine's destruction. Magneto, on the other hand, uses his powers to take control of the Statue of Liberty, literally bringing it to life and using it to attack Mister Fantastic, Hulk and Wolverine. The heroes get trapped inside the statue and make it to its head, where they encounter Mastermind and defeat him. Believing Magneto to be on Asteroid M Island, Fury sends the Thing and Captain America there, and with the help of Storm, they defeat Rhino, and Mystique is revealed to be disguising as Magneto to lure the heroes to the island while the real Magneto continues with his plan. Meanwhile, on Asteroid M, Doom's lair in outer space, Doom and Loki's plan nears completion. Iron Man, Thor and Spider-Man arrive there and defeat Magneto, but Iron Man and Thor are incapacitated in the process. Spider-Man goes on with Storm, Thing and Captain America and they defeat Doctor Doom.
With only Loki left, he reveals his elaborate scheme to harness the power of Galactus to destroy both Earth and Asgard. Loki uses a device powered by the Cosmic Shards to control Galactus as he attacks New York. With no other options left, Fury assembles the heroes and villains together in order to defeat Galactus on the S.H.I.E.L.D. Helicarrier, splitting the combined forces into several teams. In the end, Galactus and Loki are warped into a portal into space. The heroes make an agreement with the villains to give them time to escape before they are pursued.
- Differences from the game:
- They are more similar to the Marvel Cinematic Universe rather than the game.