[1] He is known for collaborating with auteur filmmakers like Paul Schrader, Abel Ferrara, Lars von Trier, Julian Schnabel, Wes Anderson, and Robert Eggers.

His other films credits include To Live and Die in L.A. (1985), The Last Temptation of Christ (1988), Born on the Fourth of July (1989), Wild at Heart (1990), The English Patient (1997), American Psycho (2000), The Life Aquatic with Steve Zissou (2004), Antichrist (2009), John Carter (2012), The Lighthouse (2019), Poor Things (2023), and Nosferatu (2024).

[10] After attending Appleton East High School, Dafoe studied drama at the University of Wisconsin–Milwaukee,[13] and left after 18 months to join the experimental theater company Theatre X in Milwaukee, before moving to New York City in 1976.

[33] Dafoe was briefly considered for the role of the super-villain the Joker in the Tim Burton-directed superhero film Batman (1989), as screenwriter Sam Hamm noticed physical similarities, but was never offered the part that eventually went to Jack Nicholson.

[34] Dafoe starred in the drama Triumph of the Spirit in 1989 as Jewish Greek boxer Salamo Arouch, an Auschwitz concentration camp inmate who was forced to fight other internees to death for the Nazi officers' entertainment.

[37] Dafoe made a cameo appearance in John Waters' musical comedy Cry-Baby (1990) as a prison guard who gives a brief lecture on values to the title character, who is played by Johnny Depp.

[47] Dafoe co-starred in the spy thriller Clear and Present Danger (1994), an adaptation of the Tom Clancy novel of the name starring Harrison Ford as operative Jack Ryan.

In 1997, Dafoe returned to playing a villainous role in the action thriller Speed 2: Cruise Control, expressing the necessity of appearing in both independent and blockbuster films.

[55] The film starred Sandra Bullock and Jason Patric as a couple vacationing on a luxury cruise that has been hijacked by Dafoe's character, Geiger, a hacker that has programmed the ship to crash into an oil tanker.

[67] He then acted in Steve Buscemi's crime drama Animal Factory, starring as an incarcerated veteran con-man who takes a young inmate (played by Edward Furlong) under his wing and introduces to him to his gang.

[72] He starred opposite Haley Joel Osment in Edges of the Lord, playing a compassionate priest helping a young Jewish boy pose as a Catholic to protect him during Nazi Germany's occupation of Poland.

[74] Dafoe's role in the film was generally well-received, including a New York Daily News reviewer who felt he put "the scare in archvillain" and Peter Bradshaw of The Guardian who deemed him "strong support".

The film takes place during the Middle Ages and saw Dafoe play the leader of acting troupe that recreate the events surrounding a woman accused of witchcraft and murder, who they believe is innocent.

[87][88] Dafoe had a small role as a tabloid magazine editor in Martin Scorsese's The Aviator (2004), a biographical film about Howard Hughes starring Leonardo DiCaprio.

[96] Dafoe had a supporting role in Spike Lee's 2006 crime thriller Inside Man, playing a veteran captain helping with a hostage negotiation during a bank heist on Wall Street.

[102] In the same year, Dafoe voiced the main villain, an evil wizard, in the English dub of the Japanese animated fantasy film Tales from Earthsea,[103] had a supporting role as a US Senator in the drama The Walker, his fourth collaboration with Paul Schrader,[104] and took on the lead role in the psychological thriller Anamorph, in which Dafoe played a detective who notices the case he is investigating bears similarities to a previous case of his.

[119] Dafoe had a voice role in Wes Anderson's stop-motion animated film Fantastic Mr. Fox starring George Clooney as the titular Roald Dahl character.

[141] In Scott Cooper's Out of the Furnace (2013), starring Christian Bale, Dafoe played the supporting role of a bookmaker running an illegal gambling operation.

[143] Also in 2013, Dafoe played the devil in a Mercedes-Benz Super Bowl commercial[144] and starred in three short student films as part of a competition sponsored by Jameson Irish Whiskey.

[145] In 2014, Dafoe portrayed a wealthy private banker with connections to the Russia mafia opposite Philip Seymour Hoffman in Anton Corbijn's espionage thriller A Most Wanted Man.

[146] Dafoe worked with Wes Anderson for a third time with the comedy The Grand Budapest Hotel (also 2014), featuring as the henchman of Adrien Brody's character alongside an ensemble cast led by Ralph Fiennes.

[147] Dafoe next starred alongside Matt Dillon as a detective in the crime thriller Bad Country, which critic Justin Chang dismissed as being "blandly constructed".

[149] He was next featured in a supporting role as a mean-spirited, alcoholic author who is visited by a pair of cancer patients, who are played by Shailene Woodley and Ansel Elgort, in the romantic drama The Fault in Our Stars.

[151] His final film of 2014 was the action thriller John Wick starring Keanu Reeves, in which Dafoe appeared as the mentor to the titular character, a former hitman who is forced out of retirement to seek vengeance for the killing of his puppy.

[158] He next played the boss of Gerard Butler's character in the drama A Family Man and starred in Loris Gréaud's arthouse science fiction film Sculpt, which was only screened at the Los Angeles County Museum of Art for one person at a time.

[161] Also in 2016, Dafoe appeared in another Super Bowl commercial, this time for Snickers, recreating Marilyn Monroe's iconic white dress scene from the film The Seven Year Itch.

[166] Also that year, he co-starred as Gerhard Hardman in a film adaptation of Agatha Christie's detective novel Murder on the Orient Express, directed by and starring Kenneth Branagh;[167] and played Atlantean scientist Nuidis Vulko in a deleted role in Zack Snyder's Justice League.

"[170] In 2019, he had a supporting role in Edward Norton's period crime drama Motherless Brooklyn where he played powerful developer Moses Randolph's "beaten and broken" brother.

[193] He starred as real-life television talent executive David Tebet in Jason Reitman's biographical comedy-drama film Saturday Night, released on October 11, 2024.

[195] He will play Maxim, the overly-protective father in the A24 fantasy adventure film The Legend of Ochi with Helena Zengel, Emily Watson, and Finn Wolfhard, set for release on February 28, 2025.