Parker was born and raised in Cleveland, Ohio, but moved to Washington, D.C. in 1987 to study at Howard University. After graduating with a Bachelor of Fine Arts degree, she moved to New York City and played a number of clubs. From 1992 to 1993, she performed on the FOX comedy program The Apollo Comedy Hour, filmed live at the legendary Apollo Theater, and later was cast member on the short-lived sketch show, Townsend Television.
In 1995, Parker made her film debut in the F. Gary Gray urban comedy Friday. In the same year, she earned a Cable ACE Award for her role in the HBO anthology presentation, Cosmic Slop. Later that year, Parker returned to television in the WB sitcom, The Wayans Bros. opposite Shawn and Marlon Wayans. Throughout the 1990s, she appeared in several short-lived shows, including CBS sitcom The Weird Al Show (1997), and David E. Kelley's ABC comedy-drama, Snoops (1999).
During the 1990s, Parker had supporting roles in a number of films. She has appeared in the 1995 horror anthology Tales from the Hood, Spike Lee's Million Man March drama Get on the Bus (1996), the urban comedy Sprung (1997), Jada Pinkett Smith starring romantic comedy Woo (1997), the Frankie Lymon biography, Why Do Fools Fall in Love (1998). In the early 2000s, Parker co-starred in 30 Years to Life, High Crimes, Phone Booth, and My Baby's Daddy. In 2004, she played the lesbian woman in the LGBT comedy-drama, She Hate Me, and appeared as Ruth Brown in biographical film Ray. Her breakthrough was in the 2005 independent drama Hustle & Flow starring Terrence Howard. She later was cast opposite Howard in musical film Idlewild (2006).

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