Horsford is best known for her roles as Thelma Frye on the NBC sitcom Amen (1986–91), and as Dee Baxter on the WB sitcom The Wayans Bros. (1995–99). She had dramatic roles on the FX crime drama The Shield playing A.D.A. Beth Encardi, and CBS daytime soap opera The Bold and the Beautiful as Vivienne Avant, for which she was nominated for the Daytime Emmy Award for Outstanding Special Guest Performer in a Drama Series in 2016 and Outstanding Supporting Actress in a Drama Series in 2017.

Horsford appeared in a number of movies, most notable as Craig Jones' mother Betty in 1995 comedy film Friday and its sequel Friday After Next (2002). Her other film credits include Times Square (1980), The Fan (1981), Presumed Innocent (1990), Set It Off (1996), Along Came a Spider (2001), Our Family Wedding (2010), and A Madea Christmas (2013).