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Hurt was born in Washington, D.C., the son of Claire Isabel (née McGill), who worked at Time, Inc., and Alfred McCord Hurt, who worked for the U.S. State Department. His mother re-married Henry Luce III (the son of the founder of Time Magazine) during Hurt's childhood. Hurt graduated from Middlesex School in 1968 where he was the Vice President of the Dramatics Club and had the lead role in several of the school plays. His high school yearbook predicted, "With characteristics such as these, you might even see him on Broadway." Hurt attended Tufts University and studied theology, but turned instead to acting and joined the Juilliard Drama School studying alongside Christopher Reeve. Hurt appeared first on stage, only later turning to film. His first major role was in the sci-fi hit Altered States (1980) which gave him wide recognition for playing an obsessed scientist. He received the Best Male Performance Prize at the Cannes Film Festival and the Academy Award for Best Actor for Kiss of the Spider Woman in 1985. He received three additional Oscar nominations; one for Children of a Lesser God (1986), one for Broadcast News (1987) and one (for Best Supporting Actor) in A History Of Violence (2005).

Often cast as an intellectual, Hurt has put this to good use in many films like Lost in Space and The Big Chill, but he is also effective in other kinds of roles like I Love You to Death, and David Cronenberg's psychological drama A History of Violence (2005), wherein, with less than 10 minutes of screen time, he plays the creepy mob boss Richie Cusack. That same year, Hurt could be seen as a mysterious government operative in Stephen Gaghan's ensemble drama about the politics of Big Oil, Syriana.

Hurt has been seen in the mini-series adaptation of Stephen King's Nightmares and Dreamscapes, in a piece entitled Battleground; he plays "Renshaw", a hitman who receives a package from the widow of a toymaker he killed, unaware of what is waiting inside for him. He is currently in the cast of "Vanya", an adaptation of Chekhov's Uncle Vanya playing in the Artist Repertoire Theatre in Portland, Oregon.

He appeared in Sean Penn's critically acclaimed film Into the Wild, the true story of Christopher McCandless and his life changing adventures. Hurt next starred as General Thaddeus "Thunderbolt" Ross in The Incredible Hulk alongside Edward Norton, Liv Tyler and Tim Roth. Fluent in French, Hurt maintains a home outside Paris. He has a daughter with actress Sandrine Bonnaire and a son, Alex, with Sandra Jennings, who sued Hurt in the late 1980s claiming she was his common-law wife. Hurt won the case. He was previously married to Mary Beth Hurt from 1971 to 1982 and lived with Marlee Matlin for a period of time in 1986. Hurt has two sons, named Sam and William Hurt, from his 1989-92 marriage to Heidi Henderson.