Mark Wingert as Tony Stark: An industrialist, genius inventor, and consummate playboy, he is the CEO of Stark Industries and chief weapons manufacturer for the U.S. military. Stark is killed in the first act.
Don Cheadle as Lieutenant Colonel James Rhodes / Iron Man: A friend of Stark's and the liaison between Stark Industries and the United States Air Force in the department of acquisitions, specifically weapons division, who, inspired by Tony's sacrifice and the first Iron Man armor uses it to become an superhero.
Beth Hoyt as Pepper Potts / Rescue: Stark's personal assistant who later becomes Rhodes' love interest.
Jeffrey Wright as Uatu the Watcher: A member of the alien Watcher race who observes the multiverse.
Kiff VandenHeuvel as Obadiah Stane / Iron Monger: Stark's business second-in-command, mentor, and friend, who turns on him to take over the company, eventually building an giant exosuit to fight Stark.
Shaun Toub as Ho Yinsen: Stark's fellow captive, who grafts an electromagnet to Stark's chest "to keep the shrapnel shell shards that wounded him from reaching his heart and killing him". After Stark's death and bravery, Yinsen builds an suit of armor ("Iron Man" Mark I) to aid in his escape and immigrates to the United States to escape death.
Faran Tahir as Raza: The leader of the Ten Rings.
Paul Bettany as J.A.R.V.I.S.: Stark's personal AI system.
Leslie Bibb as Christine Everhart: A reporter for Vanity Fair.
Clark Gregg as Phil Coulson: An agent of S.H.I.E.L.D.
Will Lyman as the voice at the ceremony
Jon Favreau as Happy Hogan: Stark's bodyguard and chauffeur. He will eventually become "War Machine" and "Iron Patriot", taking over Rhodes' role from the MCU.
Samuel L. Jackson as Nick Fury: The director of S.H.I.E.L.D.
Mike McGill as General Thaddeus Ross: The general of the United States Army who Potts and Rhodes converse with on a "team".
Stan Lee as himself: The Watcher Informant reprises his role using archive footage as he impersonates Hugh Hefner.
Peter Billingsley as William Ginter Riva: A scientist who works for Stane.
Jim Cramer as himself