- He was a candidate for the role of the Joker in Batman (1989), which went to Jack Nicholson.
- Says he feels like he has missed out on more conventional roles because he's perceived as an eccentric actor in dark little films, kind of the boy-next-door type - if you lived next door to a mausoleum.
- He was delirious for 24 hours after coming down with yellow fever on the set of Platoon (1986).
- He has appeared in six films that have been nominated for the Best Picture Oscar: Platoon (1986), Mississippi Burning (1988), Born on the Fourth of July (1989), The English Patient (1996), The Aviator (2004) and The Grand Budapest Hotel (2014). Platoon and The English Patient won in the category.
- He had done most of his own stunts on the glider in Spider-Man (2002). So when you see the Green Goblin moving around on it, when it's not CG, then it's Willem pretty much the whole time.
- Is the second youngest of eight siblings. He has five sisters, named Diane Fredrickson, Jane Lambie, Nancy Christiansen, Barbara Dafoe Whitehead, and Sarah Holbrook, and two brothers, named Richard and Donald. Brother, Donald Dafoe, is an accomplished transplant surgeon.
- His first name, William, is shared with his father. He did not want to be called William Jr. or Billy, and among various nicknames since childhood, was Willem, which he liked, and has kept this name ever since.
- Has provided his voice on Lou Reed's album "The Raven" (2003). On this, he performs a rewritten and reworked, spoken-word version of Edgar Allan Poe's poetry.
- The only actor to ever be nominated for an Academy Award for playing a vampire, for his role as Max Schrek in Shadow of the Vampire (2000).
- He was under consideration for Dennis Hopper's role (Frank Booth) in Blue Velvet (1986).
- Divides his time between Rome, New York City and Los Angeles with his Italian wife Giada Colagrande.
- Named one of "The 25 Greatest Actors of the 21st Century" by the New York Times (November 25, 2020).
- While doing a blocking run-through on Wild at Heart (1990) (for the scene in which Dafoe's character threatens to rape Laura Dern's character), Dafoe playfully sang his lines. Director David Lynch loved this, and wanted Dafoe to actually sing his lines in the scene, when they shot this. However, the idea did not actually go through.
- Built sets and worked with the experimental group Theatre X in Milwaukee, Wisconsin, before moving to New York City in 1976, where he worked with the Wooster Group at the Performing Garage which has toured America and the world.
- Quite possibly has the most on-screen deaths of any mainstream actor. His death scenes include Platoon (1986), The Last Temptation of Christ (1988), Wild at Heart (1990), Speed 2: Cruise Control (1997), eXistenZ (1999), Shadow of the Vampire (2000), Spider-Man (2002), and Once Upon a Time in Mexico (2003), among others.
- Childhood celebrity crush was sex symbol Raquel Welch.
- He sticks to an all-organic, vegan diet except for the rare occasion when he indulges in a fried lake perch sandwich.
- Was involved for decades (from 1977) with theater director and actress Elizabeth LeCompte, who was also a member and director of the Wooster Group. He later married Italian writer/director Giada Colagrande in 2005.
- Has a son with Elizabeth LeCompte: Jack Dafoe (born 1982).
- John Malkovich, Nicolas Cage and Dafoe were all approached to play the Green Goblin in Spider-Man (2002). Dafoe and Malkovich starred in Shadow of the Vampire (2000) together, while Cage produced the film. Dafoe ended up getting the Spider-Man role.
- He was offered the role of Senator Ethan Roark in Sin City (2005), which went to Powers Boothe.
- Attended and graduated from Appleton East High School in Appleton, Wisconsin.
- Has worked with seven directors who have won the Best Director Oscar: Michael Cimino, Kathryn Bigelow, William Friedkin, Oliver Stone, Martin Scorsese, Anthony Minghella and Guillermo del Toro.
- Visited the Sarajevo International Film Festival together with Steve Buscemi in 2000.
- Attended Einstein Junior High School in Appleton, Wisconsin, where he was known as "Billy".
- Member of the 'Official Competition' jury at the 57th Berlin International Film Festival in 2007.
- As a 12-year old, he attended the 1967 NFL Championship Game between the Dallas Cowboys and Green Bay Packers, better known as the Ice Bowl, one of the most famous games in pro football history.
- Speaks Italian fluently.
- The longest he has gone without an Academy Award nomination is the 17 years between Shadow of the Vampire (2000) and The Florida Project (2017).
- Member of the 'Official Competition' jury at the 67th Cannes International Film Festival in 2014.
- Was listed as a potential nominee on the 2006 Razzie Award nominating ballot. He was listed as a suggestion in the Worst Supporting Actor category for his performance in the film xXx: State of the Union (2005). However, he failed to receive a nomination (Had he gotten the nomination, it would have been his third overall. He was previously nominated for Worst Supporting Actor at the 1998 Razzie Awards for his role in Speed 2: Cruise Control (1997), and for Worst Actor at the 1994 Razzie Awards for his performance in Body of Evidence (1993).).
- Michael Cimino dismissed him from his Western epic Heaven's Gate (1980) because he laughed at a crew member's joke during production. However, he was only present for the first three months of an eight-month shoot and did not receive any credit for his work on the film.
- Has English, French, German, Irish, Northern Irish, Scottish and Swiss-French ancestry. Many of his antecedents resided in Canada.
- He has appeared in one film that has been selected for the National Film Registry by the Library of Congress as being "culturally, historically or aesthetically significant": Platoon (1986).
- On May 22, 2022, he was invited back to his alma mater the University of Wisconsin-Milwaukee (UWM) to serve as the keynote speaker for the university's commencement ceremony and to receive an honorary degree (Doctor of Arts).
- Longtime practitioner of ashtanga vinyasa yoga.
- He was awarded a Star on the Hollywood Walk of Fame at 6284 Hollywood Boulevard in Hollywood, California on January 8, 2024. Patricia Arquette and Pedro Pascal were guest speakers at the ceremony.
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