Michael Michele was born Michael Michele Williams in Evansville, Indiana, the elder of two daughters. Her father, Jerry, is Caucasian, and her mother, Theresa, is African American .[citation needed] Her father is an entrepreneur and business consultant and her mother is a corporate manager.[citation needed] In high school, Michele was active on the volleyball, basketball, and track teams. She has a son Brandon (born December 21, 2004) with boyfriend Jimmy Rodriguez.

Michele appeared in music videos, some of which were by R&B crooner Freddie Jackson. Michele is known for her role as Dr. Cleo Finch on the television series ER from 1999–2002 and her role as Det. Rene Sheppard on the final season of Homicide: Life on the Street. She also had a starring role in the short-lived television series Kevin Hill and a recurring role in New York Undercover. Michele played the role of Veronica Porsche Ali in the 2001 film, Ali. She appeared in an episode of Law & Order: Special Victims Unit, that aired in early 2007. She also appeared in two episodes in the fourth season of House as a doctor who had previously worked with the CIA.

On March 14, 2009 Michele appeared in the Hallmark Channel original movie, Relative Stranger, with fellow ER cast member Eriq La Salle.