- Robert Downey Jr. as Tony Stark / Iron Man: The leader and benefactor of the Avengers who is a self-described genius, billionaire, playboy, and philanthropist with electromechanical suits of armor of his own making.
- Chris Hemsworth as Thor: An Avenger and the king of Asgard based on the Norse mythological deity of the same name.
- Mark Ruffalo as Bruce Banner / Hulk: An Avenger and a genius scientist who, because of exposure to gamma radiation, transforms into a monster when enraged or agitated.
- Chris Evans as Steve Rogers: The fugitive superhero formerly known as Captain America, leader of a faction of Avengers.
- Scarlett Johansson as Natasha Romanoff / Black Widow: A highly trained spy, and former Avenger and agent of S.H.I.E.L.D.
- Benedict Cumberbatch as Stephen Strange: A former neurosurgeon who, after a car accident that led to a journey of healing, discovered the hidden world of magic and alternate dimensions and became a Master of the Mystic Arts.
- Don Cheadle as James "Rhodey" Rhodes / War Machine: A former officer in the U.S. Air Force who operates the War Machine armor and is an Avenger.
- Tom Holland as Peter Parker / Spider-Man: A teenager and Stark's protegé who received spider-like abilities after being bitten by a genetically-modified spider.
- Chadwick Boseman as T'Challa / Black Panther: The king of the African nation of Wakanda, who gained his enhanced strength by ingesting the Heart-Shaped Herb.
- Paul Bettany as Vision: An android and Avenger created using the artificial intelligence J.A.R.V.I.S. and the Mind Stone.
- Elizabeth Olsen as Wanda Maximoff / Scarlet Witch: A member of Rogers' faction of Avengers, who can harness magic and engage in hypnosis and telekinesis.
- Anthony Mackie as Sam Wilson / Falcon: A member of Rogers' faction of Avengers and former pararescueman trained by the military in aerial combat using a specially designed wing pack.
- Sebastian Stan as Bucky Barnes / White Wolf: An enhanced assassin and Rogers' ally and best friend, who reemerged brainwashed after being thought killed in action during World War II.
- Benedict Wong as Wong: One of the Masters of the Mystic Arts, tasked with protecting some of Kamar-Taj's most valuable relics and books.
- Pom Klementieff as Mantis: A member of the Guardians of the Galaxy with empathic powers.
- Karen Gillan as Nebula: An adopted daughter of Thanos who was raised with Gamora as siblings.
- Dave Bautista as Drax the Destroyer: A member of the Guardians and warrior in search of vengeance against Thanos for killing his family.
- Zoe Saldana as Gamora: A member of the Guardians who is an orphan from an alien world who seeks redemption for her past crimes. She was raised by Thanos.
- Chris Pratt as Peter Quill / Star-Lord: The half-human, half-Celestial leader of the Guardians who was abducted from Earth as a child and raised by a group of alien thieves and smugglers called the Ravagers
- Benicio del Toro as Taneleer Tivan / The Collector: An obsessive keeper of the largest collection of interstellar fauna, relics, and species of all manner in the galaxy.
- Josh Brolin as Thanos: An intergalactic despot from Titan who longs to collect all of the Infinity Stones in order to impose his will on all of reality,
Two years after the Avengers were torn apart during the events of Captain America: Civil War, Thanos arrives on Earth to collect the Infinity Stones for a gauntlet that will allow him to bend reality to his will. The Avengers must join forces with the Guardians of the Galaxy to stop him before his onslaught of destruction puts an end to half the universe.
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