Isaiah Washington IV was born on August 3, 1963 in Houston, Texas. Washington reportedly took a DNA test to determine his heritage and it showed that his father's side is Angolan and his mother's side is from Sierra Leone.

Washington was one of the first graduates from Willowridge High School, Houston, in 1981. He served in the United States Air Force prior to beginning a career as a professional actor.

Washington's film credits are vast and include: The Color of Love, Land Where My Fathers Died, Strictly Business, Alma's Rainbow, Crooklyn, Stonewall, Clockers, Dead Presidents, Girl 6, Get on the Bus, Love Jones, Mixing Nia, Bulworth, Rituals, Out of Sight, True Crime, A Texas Funeral, Veil, Dancing in September, Romeo Must Die, Kin, Tara, Exit Wounds, Sacred Is the Flesh, Welcome to Collinwood, Ghost Ship, Hollywood Homicide, This Girl's Life, Blood on a Happy Face, Wild Things 2, Dead Birds, Trois: The Escort, and The Moguls.

One television, Washington has starred on Grey's Anatomy as Dr. Preston Burke.