Eric Roberts was born in Biloxi, Mississippi. Roberts's parents, one-time actors and playwrights, met while performing theatrical productions for the armed forces and later co-founded the Atlanta Actors and Writers Workshop in Atlanta, Georgia; the two divorced in 1971. His younger siblings, Julia Robertsand Lisa Roberts Gillan, are also actors. Eric was raised in Atlanta, Georgia and attended Grady High School.

Roberts received Golden Globe nominations for his early starring roles in King of the Gypsies (1978) and Star 80 (1983). He was nominated for the Academy Award for Best Supporting Actor in 1985 for his role as the escaped convict Buck in the film Runaway Train. In 1987, he won the Theatre World Award for his Broadway debut performance in Burn This.

Roberts's other starring roles included Raggedy Man (1981), The Pope of Greenwich Village (1984), The Coca-Cola Kid (1985), Rude Awakening (1988), Best of the Best (1989), By the Sword (1991), Best of the Best 2 (1993), The Specialist (1994), The Immortals (1995), La Cucaracha (1998), Purgatory (1999), and Con Games (2001). He played the Archangel Michael in The Prophecy II (1979).

In 1996, he appeared in the Doctor Who TV movie in the role of the Master. As of 2008, he is the only American actor to ever play this role.

He also appears in the 2000 film Race Against Time as a father who sells his organs to pay for hospital treatment for his son and in the 2003 film Spun as "The Man" alongside Mickey Rourke and Jason Schwartzmann. He performed the voice of Dark Danny in Nickelodeon's Danny Phantom. He made a cameo appearance in The Cable Guy.

Roberts starred in Royal Kill, a psychological thriller that also stars Pat Morita, Lalaine, and Gail Kim and is directed by Babar Ahmed. He appeared as a panelist on the television game show Hollywood Squares. Roberts co-starred on the Abcsitcom Less Than Perfect. In 2006, Roberts appeared in the film A Guide to Recognizing Your Saints. In the same year, he was also guest starred on The L Word as Shane McCutcheon's father, Gabriel.

He appeared in the 2007 action film DOA: Dead or Alive. He was in the Batman Begins sequel, The Dark Knight, as Sal Maroni, an organized crime boss.

Roberts appeared in The Killers' music video for their song "Mr. Brightside" as well as in the music videos for Mariah Carey's "We Belong Together" and "It's Like That". In 2006, he appeared in the video for Akon's "Smack That", featuring Eminem. In 2007, he appeared in the video for Godhead's "Hey You".

He appeared in an episode of CSI: Miami as Ken Kramer, a murderer on death row convicted of killing a young couple. Another notable TV appearance was the episode "Victims" of Law & Order: Special Victims Unit where he played Sam Winfield, a former cop turned vigilante community activist. In early January 2007, Roberts starred in the two-part mini-series Pandemic as the mayor of Los Angeles.