- After acting in Hotel Ruanda (2004), a film about the early 1990s Rwandan genocide, he became an activist to raise awareness of the mid-2000s genocide in the Darfur region of Sudan. In January 2005, he traveled to Sudan with five members of Congress to see refugee camps and to meet survivors of the genocide. Upon his return, he reported on his trip for ABC News Nightline (1979).
- Plays the saxophone.
- During the making of Missão: Marte (2000), he asked to sleep overnight on the film set so that he could stay in full character.
- Briefly worked as a stand-up comic early in his career.
- Appeared in Os Maiorais (1998) as Sammy Davis Jr., who along with the other Rat Pack members, appeared in the original Onze Homens e um Segredo (1960). Cheadle then appeared in the remake, Onze Homens e um Segredo (2001).
- Was considered for the role of Huggy Bear in the movie Starsky & Hutch, Justiça em Dobro (2004).
- Got his first big break starring as the hotel clerk on the short lived-Super Gatas (1985) spin-off The Golden Palace (1992) alongside Cheech Marin.
- Replaced Terrence Howard in the role of Col. James Rhodes for Homem de Ferro 2 (2010). Howard, who had played Rhodes in Homem de Ferro (2008), had a falling out with Marvel Studios because of a salary dispute.
- Appears uncredited in two back-to-back movies, A Hora do Rush 2 (2001) and Onze Homens e um Segredo (2001). He played a criminal in both films.
- He and Bridgid Coulter have two daughters, Ayana and Imani (born in 1995 and 1997).
- Hotel Ruanda (2004) is ranked #90 on the American Film Institute's 100 Most Inspiring Movies of All Time, the most recent entry on the list.
- His sister is a teacher in Washington, D.C.; and their brother works in Denver's mayor's office.
- In July 2005, he officially toured the Hotel des Milles Collines in Kigali, Rwanda, on which the film Hotel Ruanda (2004) is based.
- Lives with Bridgid Coulter, who plays his wife in O Massacre de Rosewood (1997). (1997)
- The son of a child psychologist and a teacher.
- Graduated from East High School in Denver, Colorado.
- When he was younger he performed with the Colorado Children's Chorale of Denver, Colorado.
- Don Cheadle and his wife Bridgid Coulter Cheadle were among the producers who won the Tony Award for Best Play (2022) for "A Strange Loop".
- Friends with George Clooney.
- Brother of Colin Cheadle and Cindy Cheadle.
- Drives a hybrid car, a Toyota Prius.
- Appearing in promotional advertisements for the National Football League (USA) and the race to its championship title game, Super Bowl XXXVIII. (janeiro de 2004)
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