During the 1960s and 1970s, he began to take a liking towards comedy. During that time he began his stand-up comedy career. As a result, he had many friends in the business, including Tim Reid (while he was working on WKRP in Cincinnati and The Richard Pryor Show), Robin Williams (also on The Richard Pryor Show), Jay Leno, and David Letterman. Best known for his role as Willie Jones in the Friday films, Witherspoon also starred in films such as Hollywood Shuffle, Boomerang, Vampire in Brooklyn, and The Five Heartbeats. He has even made appearances on television shows, such as The Wayans Bros., The Tracy Morgan Show, Barnaby Jones, and The Boondocks.
For Disney, he voiced Oran Jones in The Proud Family, S. Ward Smith in Randy Cunningham: 9th Grade Ninja, and Wade's Uncle Wayne in Kim Possible. He also played Roscoe in Ride and Mr. Mimm in I Got the Hook Up.