Wilson was born in Houston, Texas. She started her theater career at the age of five with the Houston-based Theatre Under the Stars (TUTS). Wilson attended Houston's High School for the Performing and Visual Arts and went on to the Tisch School of the Arts at New York University, where she earned a BFA in drama.

Wilson's first notable TV role was in the short-lived series Bob Patterson (2001), one of the first post-"Seinfeld" vehicles for Jason Alexander She has also appeared on Law & Order, Sex and the City, and The Sopranos, and had a featured role in Lone Star (1996). Wilson has had a notable career in the theater. She had an acclaimed run as Bonna Willis in The Good Times are Killing Me, and was also featured in the Tony-nominated Caroline, or Change. Wilson is an accomplished singer, and has sung in several productions.

Wilson was working at a bank when she auditioned for the role of Miranda Bailey for the pilot of Grey's Anatomy. The role was initially envisioned as a blond Caucasian woman, but Wilson's audition got her cast in the role. The show became a breakout hit, and the character of Bailey - referred to as "the Nazi" - is an audience favorite. Wilson was nominated in 2006 and 2007 for an Emmy Award for best supporting actress in a drama. She was nominated and won the Screen Actors Guild Award in 2007 for outstanding female actor in a drama series; she also won a SAG Award as part of the Grey's Anatomy cast, which won Best Ensemble in a Drama Series.

Wilson and her husband have three children; daughters Serena and Joy were born in 1992 and 1994, respectively, and son Michael was born on October 31, 2005.