Del Toro made his film debut in Big Top Pee-wee (1988) before his breakout role playing an unintelligible crook in the crime thriller The Usual Suspects (1995), followed by roles in Basquiat (1996), Fear and Loathing in Las Vegas (1998), and Snatch (2000). He received the Academy Award for Best Supporting Actor for his role as a morally upright police officer in the Steven Soderbergh crime drama Traffic (2000). He was nominated in the same category for his role as an ex-con in Alejandro González Iñárritu's thriller 21 Grams (2003). He has since acted in Sin City (2005), Che (2008), Savages (2012), Inherent Vice (2014), Sicario (2015), No Sudden Move (2021), and One Battle After Another (2025).
He also took on franchise roles such as Lawrence Talbot in The Wolfman (2010), the Collector in three films from 2013 to 2018 in the Marvel Cinematic Universe, and DJ, the codebreaker, in Star Wars: The Last Jedi (2017). He also acted in the Wes Anderson films The French Dispatch (2021) and The Phoenician Scheme (2025). On television, he portrayed Richard Matt in the Showtime miniseries Escape at Dannemora (2018), for which he received a nomination for the Primetime Emmy Award for Outstanding Lead Actor in a Limited Series or Movie.
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