Hurt studied at the Juilliard School before his film debut, in Ken Russell's science-fiction feature Altered States (1980), for which he received a nomination for the Golden Globe Award for New Star of the Year.

He starred in films such as Body Heat (1981), The Big Chill (1983), The Accidental Tourist (1988), Alice (1990), One True Thing (1998), Syriana (2005), Mr. Brooks (2007) Into the Wild (2007), and The Yellow Handkerchief (2008).

He portrayed Thaddeus Ross in five of the Marvel Cinematic Universe (MCU) films starting with The Incredible Hulk (2008) and concluding with Black Widow (2021).

On television, he received Primetime Emmy Award nominations for Outstanding Supporting Actor in a Drama Series playing a scientist in the FX legal drama Damages (2009) and for Outstanding Lead Actor in a Limited Series or Movie for his portrayal of Henry Paulson in the HBO movie Too Big to Fail (2011).

On stage, Hurt appeared in off-Broadway productions of William Shakespeare's Henry V (1975), and A Midsummer Night's Dream (1982) as well as Lanford Wilson's Fifth of July (1978).

Hurt attended Tufts University and studied theology,[8][9] but turned instead to acting and joined the Juilliard School (Drama Division Group 5: 1972–1976).

His performance opposite newcomer Kathleen Turner in Lawrence Kasdan's neo-noir film Body Heat (1981) elevated Hurt to stardom.

In the 1980s, Hurt received three consecutive Academy Award nominations for Best Actor, beginning with an Oscar win for his turn as a prisoner in Hector Babenco's drama Kiss of the Spider Woman in 1985.

The New York Times wrote, "Mr. Hurt won a well-deserved best actor award at the Cannes Film Festival for a performance that is crafty at first, carefully nurtured and finally stirring in profound, unanticipated ways... What starts out as a campy, facetious catalog of Hollywood trivia becomes an extraordinarily moving film about manhood, heroism and love.

Hurt starred in the Sci Fi Channel miniseries adaptation Frank Herbert's Dune in 2000, playing Duke Leto Atreides; it was one of Syfy's highest-rated series ever.

[17] In June 2007, Marvel Studios announced that Hurt would portray General Thaddeus "Thunderbolt" Ross in the 2008 film The Incredible Hulk alongside Edward Norton, Liv Tyler, and Tim Roth.

In September 2010, Hurt played United States Secretary of the Treasury Henry Paulson in the HBO film Too Big to Fail, an adaptation of Andrew Ross Sorkin's book.

[32] In her 2009 autobiography I'll Scream Later, Marlee Matlin said that their relationship involved drug use and physical violence from Hurt,[33] including a rape.

Many actors paid tribute to Hurt, including Chris Evans, Robert Downey, Jr., Gwyneth Paltrow, Tom Hanks, Rita Wilson, Dennis Quaid, Marg Helgenberger, Kevin Costner, Russell Crowe, John Goodman, Patton Oswalt, Albert Brooks, Bryce Dallas Howard, Maria Bello, Jonathan Frakes, Ben Stiller, Mark Ruffalo, Jennifer Garner, Jeremy Renner, and Topher Grace.