- Was diagnosed with Type 2 diabetes in early 2013.
- Brother of Dwayne Wayans, Keenen Ivory Wayans, Kim Wayans, Nadia Wayans, Marlon Wayans and Shawn Wayans. Cousin of Craig Wayans. Also has three additional sisters: Elvira Wayans, Diedra Wayans and Devonne Wayans.
- Attended and graduated from Murry Bergtraum High School in Manhattan, New York City.
- Michael Kyle, his character on My Wife and Kids (2000), was ranked #27 in TV Guide's list of the "50 Greatest TV Dads of All Time" [20 June 2004 issue].
- Friends with Michael Jordan and Jim Carrey.
- Father of Damon Wayans Jr. (born 1982), Michael Wayans (born 1985), Cara Mia Wayans (born 1987), and Kyla Wayans (born 1991). Uncle of Damien Dante Wayans.
- While filming Earth Girls Are Easy (1988), this took approximately 2-1/2 hours for him and co-stars Jeff Goldblum and Jim Carrey to be suited up as the aliens.
- Only Wayans brother to not be involved in the Scary movie series.
- Along with co-stars Jeff Goldblum and Jim Carrey, his voice was dubbed in certain scenes for Earth Girls Are Easy (1988).
- Is the author of "Bootleg", a humorous compilation of his own observations with regards to family, children, marriage and politics. The book quickly reached the New York Times Bestseller List (1999).
- Has seven grandchildren. Granddaughter, Ava Marie Jean, was born February 13, 2014.
- He has appeared in two films that have been selected for the National Film Registry by the Library of Congress as being "culturally, historically or aesthetically" significant: Beverly Hills Cop (1984) and Bamboozled (2000).
- Attended Murry Bergtraum High School alongside John Leguizamo.
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