During his stint as a young student at UCLA's School of Theater, Film & Television, Charles Burnett submitted a thesis film, Killer of Sheep, which later became the basis for his first professional film effort. Burnett directed, produced, wrote, edited and acted as cinematographer on the feature, which was among the first 50 films placed in the National Film Registry because of its historical significance, and was declared a "national treasure" by the Library of Congress.

In 1983, the Vicksburg, Mississippi native wrote, directed and produced his next feature, My Brother's Wedding, a low-budget independent film centering on the theme of envy and its power to warp families. Burnett's themes of family continued to influence his work. In 1990, he wrote and directed the drama To Sleep with Anger , which starred Danny Glover as the charming, Southern family friend, 'Harry,' who insinuates himself into a troubled family, forcing their inner turmoils to the surface. The film won three 1991 Independent Spirit Awards: Best Director and Best Screenplay for Burnett, and Best Actor for Glover. In 1990, the National Society of Film Critics recognized Burnett with its award for Best Screenplay. The film also received a Special Jury Recognition Award at the 1990 Sundance Film Festival and a Special Award from the Los Angeles Film Critics Association. Both Burnett and Glover were nominated for New York Film Critics Circle Awards.

His next film, The Glass Shield, starring Lori Petty, Michael Boatman and Ice Cube, was a police drama based on a true story of corruption and racism within the Los Angeles police force. Burnett followed with his television debut via the acclaimed 1996 Disney Channel film, Nightjohn, starring Carl Lumbly, Lorraine Toussaint, Allison Jones, and Bill Cobbs. Based on the young-adult novel by Gary Paulsen, Nightjohn is a period piece about a slave's risky attempt to teach an orphan slave girl to read and write. The New Yorker's film critic Terrence Rafferty called Nightjohn the "best American movie of 1996." The film received a 1997 Special Citation Award from the National Society of Film Critics "for a film whose exceptional quality and origin challenge strictures of the movie marketplace."

Burnett's other television work includes the 1997 ABC mini-series Oprah Winfrey Presents: The Wedding, starring Halle Berry and Lynn Whitfield; the 1998 ABC telepic, Selma, Lord, Selma, starring Jurnee Smollett, Mackenzie Astin and Clifton Powell; America Becoming, a documentary about U.S. immigration; the 1998 Showtime film Long Distance; and the 2000 Showtime film Finding Buck McHenry, starring Ossie Davis.

In 1997, the Film Society of Lincoln Center and the Human Rights Watch International Film Festival honored Burnett with a retrospective of his work presented at the Walter Reade Theater at Lincoln Center. He is also the recipient of a 1988 MacArthur Foundation Fellowship. A one-time trumpet player, Burnett vividly remembers making his way through the seminal blues tunes of W.C. Handy.