Djimon's film debut was in Without You I’m Nothing, and he has had television parts on Beverly Hills, 90210 and ER and a guest starring role on Alias, but received a larger role in the science fiction film Stargate. His first on-screen appearance was in the 1990 Janet Jackson video “Love Will Never Do (Without You)”, which co-starred Antonio Sabato, Jr. He also starred in a 2002 Gap commercial directed by Peter Lindbergh, dancing to a rendition of John Lee Hooker's "Boom Boom" by Arrested Development's Baba Oje.

He received wide critical acclaim and a Golden Globe Award nomination for his role as Cinqué in the 1997 Steven Spielberg film Amistad. He gained further notice as Juba, in the 2000 film Gladiator. He was nominated for the Academy Award for Best Supporting Actor, for In America, in 2004, becoming the first black African to be nominated for an Oscar. That same year, Charlize Theron, a South African actress was nominated for her work in Monster, and was the first