She got her big break playing the role of Vanessa "Nessa" Thomkins on The Bernie Mac Show. During her run on the show Winbush earned numerous award nominations for her role, winning three NAACP Image Awards for Outstanding Supporting Actress in a Comedy Series and a Young Artist Award for Best Performance in a TV Series (Comedy or Drama) - Leading Young Actress. In 2007, she appeared in an episode of Grey's Anatomy.
In 2002, Winbush recorded "One Small Voice" featuring singers Myra & Taylor Momsen and "The Night Before Christmas Song" for the compilation album School's Out! Christmas. She also sang on the soundtrack of the Disney musical production of Geppetto.