Born in Brooklyn, New York City to Carl and Joyce Lewis, who are of African-American and Guyanese descent, Lewis began singing at the age of four and acting at eleven. Lewis graduated from the High School of Music and Art (now known as Fiorello H. LaGuardia High School) at age 16. After high school, she studied at the University of Miami, graduating cum laude with a major in Musical Theatre and a minor in Journalism in 1982.

In September 1992, Lewis began starring in ABC's Hangin' with Mr. Cooper alongside Mark Curry and Holly Robinson. Lewis appeared in 20 of the 22 episodes of the first season as Robin Dumars, Mark's childhood best friend and roommate. Lewis did not appear on the two shows concurrently — she left A Different World to star in Hangin' with Mr. Cooper. Lewis and Holly Robinson, along with R&B quartet En Vogue, performed the theme song for season one of Hangin' with Mr. Cooper. Sometime before the end of season one, The show producers decided to scale back on the updated version of the 1970s ABC sitcom Three's Company concept. Lewis left the show after the conclusion of the first season due to the producers deciding to change the direction of the show, Replacing her character with a mother and child; Mark's cousin Geneva Lee (portrayed by Saundra Quarterman) and her daughter Nicole (portrayed by Raven-Symoné).

Lewis has been married once, to former NBA player Johnny Newman from 2004 until 2006.

In 2006, Lewis starred as Melba Early in the film adaptation of Dreamgirls. Lewis released her debut CD, entitled Worth Waiting For, in 2006. She most recently played Addaperle in The Wiz with New York City Center's Encores! In 2009, Lewis played Denise Fields on One Tree Hill. In 2010, Lewis played a minor recurriung role as Lauren's mother in The Secret Life of the American Teenager. In 2012, she voiced Malora in Strange Frame. She also appeared as Dr. Knapp on Days of Our Lives in 2012–2013. As of 2015, Lewis is playing a recurring role on Major Crimes as Patrice, a love interest for Lt. Provenza, whom he met during a case. In March 2016, Lewis joined the vocal cast of Disney Junior's hit animated series Doc McStuffins as the voice of Grandma McStuffins. In 2017 she provided the voice of Maybelle Mundy in the film Bunyan and Babe.

Lewis appeared for the first five of the six-season run as Jaleesa Vinson (later Vinson–Taylor) from 1987 until 1992. Lewis co-wrote the theme song to A Different World, with Bill Cosby and Stu Gardner, and co-performed the song for the first season. In A Different World, Although her character was married to another of the main characters on the show, her character disappeared from A Different World without explanation, like Chuck Cunningham of Happy Days. Lewis appeared in a special week-long segment of A Different World called the Hillman College Reunion airing on Nick At Nite, along with Lisa Bonet, Jasmine Guy, Kadeem Hardison, Darryl M. Bell, Cree Summer, and Sinbad. On her Super Password appearance in 1988, she was paired with Dallas (1978 TV series) star Ken Kercheval, not any of her co-stars.