Foxx's parents separated soon after his birth, and he was adopted by his maternal grandparents. He began playing piano about age five and became keenly interested in music, later earning a scholarship to United States International University (now Alliant International University) in San Diego to study classical piano and music theory. It was while Foxx was a student in San Diego that he began performing at local comedy clubs. At open-microphone nights he delighted audiences with his bitingly funny impersonations of former U.S. president Ronald Reagan (Reagan, Ronald W.), boxer Mike Tyson (Tyson, Mike), and comedian Bill Cosby (Cosby, Bill). Foxx discovered, however, that it was easier for women to get stage time at open-microphone nights, so he adopted the gender-neutral name of Jamie Foxx. In 1991 Foxx won the Bay Area Black Comedy Competition, which led to an audition for the Fox television network's hit show In Living Color. His impersonations and his drag character Wanda, an ugly yet sexually aggressive woman, impressed the show's creator and star, Keenen Ivory Wayans, and earned Foxx a job as a regular. At that time Foxx also had a recurring role on the sitcom Roc.

Foxx's success on television led to new opportunities in music, television, and film. In 1994 he released his debut album, Peep This, which he also produced and composed. Two years later he landed his own television sitcom, The Jamie Foxx Show, which lasted five seasons. Foxx's first feature role in a movie was in the sex comedy Booty Call (1997), but his breakthrough performance came with Any Given Sunday (1999), in which Foxx played a young quarterback who is outwardly cocky but terrified of failure. That performance, along with his role as cornerman Drew (“Bundini”) Brown in the biopic Ali (2001), showed that Foxx's acting abilities extended well beyond simple comedic impersonations.