Born and raised in New York City by Panamanian parents,[3] Melissa De Sousa attended the High School of Performing Arts as a ballet major,[2] and began her career as a principal dancer with The Alvin Ailey American Dance Company before transitioning into acting.
She later made guest-starring appearances on Living Single, Getting By, Silk Stalkings, The Sinbad Show, Married with Children, ER and The Wayans Bros..
[4][5] In 1999, De Sousa starred as Shelby in the comedy-drama film The Best Man receiving NAACP Image Award for Outstanding Supporting Actress in a Motion Picture nomination for her performance.
[10] The following year she had recurring role as Mirta Herrera in the Showtime comedy series On Becoming a God in Central Florida.
In 2021, De Sousa had a recurring role in the final season of CW superhero series Black Lightning as Police Chief Ana Lopez.