He was best known as a writer and cast member of the Comedy Central sketch-comedy series Chappelle's Show as well as the co-star of the sitcom Black Jesus.

Murphy had minor roles in several films in the late 1980s and early 1990s and worked behind the scenes with hip hop group K-9 Posse, a duo composed of his half-brother Vernon Lynch Jr. and Wardell Mahone.

In these, Murphy recounts his misadventures as part of his brother's entourage, including encounters with various celebrities such as Rick James and Prince.

In the film, Murphy portrayed Herb, a gay ex-con who is hired by King (Anderson) to fake his kidnapping.

[11] Murphy also did voiceovers for Budweiser radio commercials, provided the voice for Iraq War veteran/criminal Ed Wuncler III on Cartoon Network's Adult Swim series The Boondocks, and the voice for a pimp named Jizzy-B in Grand Theft Auto: San Andreas and as an albino Black graffiti artist named White Mike in Marc Ecko's Getting Up: Contents Under Pressure.

Murphy provided the voice for Spock on the G4TV's Star Trek 2.0 shorts, and the dog in his younger brother Eddie's 2007 film, Norbit.