Don Cheadle as James "Rhodey" Rhodes / Iron Man: An former officer in the U.S. Air Force and former co-CEO of Stark Industries, and Potts' boyfriend.
Beth Hoyt as Pepper Potts / Iron Woman: Tony Stark's former assistant and former co-CEO of Stark Industries, and Rhodes' girlfriend.
Jon Favreau as Happy Hogan / Iron Patriot: Tony Stark's former chauffeur and bodyguard and an officer in the Air Force, who pilots the Iron Patriot suit. Hogan was previously branded as the War Machine, but was rebranded to act more patriotic.
Guy Pearce as Aldrich Killian: The creator of the Extremis virus and the founder and owner of the science and development organization Advanced Idea Mechanics (A.I.M.), who adopts the mantle of the Mandarin as his own. Killian develops Extremis to cure his own debilitating disability; in addition to his regenerative healing qualities, he has superhuman strength and the ability to generate extreme heat. Prolonged exposure to Extremis also grants him the ability to breathe fire. Pearce reprises his role from Iron Man 3 (2013).
Rebecca Hall as Maya Hansen: A geneticist whose work helped Killian create Extremis. Hall reprises his role from Iron Man 3 (2013).
Stéphanie Szostak as Ellen Brandt: A war veteran who becomes an assassin after her exposure to Extremis. Szostak reprises her role from Iron Man 3 (2013).
James Badge Dale as Eric Savin: Killian's Extremis-powered henchman. Dale reprises his role from Iron Man 3 (2013).
William Sadler as Matthew Ellis: The President of the United States. Sadler reprises his role from previous MCU media.
Miguel Ferrer as Rodriguez: The Vice President of the United States secretly working with A.I.M. Ferrer reprises his role from Iron Man 3 (2013).
Walt Hadfield: A former architect and Rhodes and Potts' former chauffeur and bodyguard, who now serves as Stark Industries' head of security.
Ben Kingsley as Trevor Slattery / Mandarin: A British actor whom Killian hired to portray the Mandarin, a terrorist persona in jammed television broadcasts in which he is depicted as the leader of the international terrorist organization the Ten Rings. Kingsley reprises his role from previous MCU media.
Paul Bettany as J.A.R.V.I.S.: Rhodes and Potts' artificial intelligence (AI) system, who powers their suits.
Ty Simpkins as Harley Keener: A child who lives in Rose Hill, Tennessee who assists Rhodes and Potts after they break into his garage to repair their suits. Simpkins reprises his role from previous MCU media.
Ashley Hamilton as Taggert: One of the Extremis soldiers. Hamilton reprises her role from Iron Man 3 (2013).
Adam Pally as Gary: A cameraman who helps Rhodes and Potts. Pally reprises his role from Iron Man 3 (2013).
Shaun Toub as Yinsen: An Afghanistan engineer and scientist, who developed the Arc Reactor and original Iron Man armor.
Stan Lee as a pageant judge: A pageant judge at a Christmas beauty pageant.
Dale Dickey as Mrs. Davis: The mother of an Extremis subject that is labeled as a terrorist attack. Dickey reprises her role from Iron Man 3 (2013).
Wang Xeuqi as Dr. Wu: A heart surgeon. Xeuqi reprises his role from Iron Man 3 (2013).
Jenny Ortega as Rodriguez's daughter: Rodriguez's daughter, who suffers from a genetic disease where her leg had to be amputated. Ortega reprises her role from Iron Man 3 (2013).
Mark Ruffalo as Bruce Banner / Hulk: A genius scientist, who when enraged or agitated, turns into a green-skinned monster.
Benicio del Toro as Taneleer Tivan / The Collector: A collector of exotic flora and fauna. Toro reprises his role from previous MCU media.
Ophelia Lovibond as Carina: Tivan's slave, who introduces guests to him. Lovibond reprises her role from previous MCU media.
Ray Stevenson as Volstagg: A member of the Three Warriors, who tends to eat more than the average person. Stevenson reprises his role from previous MCU media.
Jaimie Alexander as Sif: Thor's childhood friend, who has an unrequited crush on him. Alexander reprises her role from previous MCU media.
Natalie Portman as Jane Foster: An astrophysicist and Thor's girlfriend. Portman reprises her role from previous MCU media.
Stellan Skarsgård as Erik Selvig: An astrophysicist and Jane's mentor.
Kat Dennings as Darcy Lewis: A college student studying political science and Jane's intern. Dennings reprises her role from previous MCU media.
Chris Hemsworth as Thor: The crown prince of Asgard and Avenger, based on the Norse mythological deity of the same name.
Thomas Kretschmann as Baron Wolfgang von Strucker: The leader of Hydra's cell in Sokovia. Kretschmann reprises his role from previous MCU media.
Henry Goodman as List: A Hydra scientist who experiments on Wanda and Pietro. Goodman reprises his role from previous MCU media.
Wanda Maximoff: A volunteer for Hydra's experiments, who can engage in telekinesis, hypnosis, and reality-warping abilities.
Pietro Maximoff: A volunteer for Hydra's experiments, who can run at superhuman speeds.
Bucky Barnes / Winter Soldier: Steve Rogers' best friend and a World War II veteran thought killed in action before re-emerging as a brainwashed super-assassin.
Seth Green as Howard the Duck: An anthropomorphic duck from Tivan's collection. Green reprises his role from previous MCU media.
Cosmo the Spacedog: An anthropomorphic dog from Tivan's collection.