Damon starred doing stand-up comedy in 1982. His earliest film appearance was a brief cameo as a hotel employee in Beverly Hills Cop. He was briefly on Saturday Night Live as a featured performer, until he was fired for portraying a flamboyant gay cop instead of a straight cop in a live skit. After that he went on to co-create and star in In Living Color. In 1996, he produced a cartoon series called Waynehead, which aired on WB, loosely based on his childhood life. In 1998, Damon starred in a short-lived comedy titled, Damon, but only lasted one season. In 2005, he starred as the role of Michael Kyle in the series, My Wife and Kids which aired 5 seasons. Damon created his own sketch-comedy series, The Underground, but was cancelled with only one season. Damon also has a untitled project that is soon to be announced.
Damon was married to Lisa Thorner, until they divorced in 2000. Damon has four children, Damon Wayans, Jr., Michael Wayans, Cara Mia Wayans, and Kyla Wayans. He won the People's Choice Awards for favorite male. Damon was also born with club foot. Damon also announced during a show that he was diagnosed with Type 2 Diabetes.