Washington began his career collaborating with director Spike Lee on the films Crooklyn (1994), Clockers (1995), Girl 6 (1996), and Get on the Bus (1996).

He also appeared in the films Love Jones (1997), Bulworth (1998), Out of Sight (1998), True Crime (1999), Romeo Must Die (2000), Exit Wounds (2001), Ghost Ship (2002), and Hollywood Homicide (2003).

He was dismissed after the third season due to his usage of a homophobic slur while referring to a cast member, T. R. Knight, although he would return for a guest appearance in 2014.

Washington made his feature film debut in 1991's Strictly Business before engaging in a string of collaborations with director Spike Lee.

He also had roles in the films Stonewall, Dead Presidents, Love Jones, Out of Sight, Bulworth, True Crime, Romeo Must Die, Exit Wounds, Hollywood Homicide, and Wild Things 2.

In 2005, Washington originated the role of gifted cardiothoracic surgeon Dr. Preston Burke on the ABC medical drama Grey's Anatomy.

In October 2006, rumors surfaced that Washington allegedly insulted co-star T. R. Knight with a homophobic slur while arguing with Patrick Dempsey.

On January 30, 2007, a source told People magazine that Washington was scheduled to return to the Grey's Anatomy set as early as that Thursday for the first time since entering "executive counseling" after making the comments at the Golden Globes.

"I'm mad as hell and I'm not going to take it anymore," Washington said in a statement released by his publicist (borrowing the famous line from Network).

NBC co-chairman Ben Silverman noted his eagerness to work with Washington, saying it would be "like A-Rod leaving the Yankees in midseason".

Washington portrayed perpetrator John Allen Muhammad, with Tequan Richmond playing Muhammed's accomplice Lee Boyd Malvo.

He has written a book called A Man from Another Land, which chronicles Washington's early life, his TV and film career, and his search to find his roots after going through a DNA test that showed his ancestors came from Sierra Leone in West Africa.

Since learning about his history, Washington has traveled to Sierra Leone, donated medical supplies to a hospital there, and built a school.

[19] He has also been vested with a chieftaincy title of the Mende people in appreciation for his work in the country, taking the regnal name of Gondobay Manga II.