Stewart's early career also included notable work as a voice actor. He provided the narration for "Scenes in the City", a long jazz composition with a text by Lonne Elder and Langston Hughes that appeared on Charles Mingus' 1957 album A Modern Jazz Symposium of Music and Poetry. In 1961, Stewart recorded an album of Langston Hughes' poetry on Folkways Records: Langston Hughes' The Best of Simple. He was also a member of the San Francisco-based improv group, The Committee and appeared in 1969 on The Dick Cavett Show.

Mel Stewart began his acting career in 1959 with small roles in TV and films. In the early 1960s, Stewart also appeared in the Broadway shows Purlie Victorious, The Hostage, The Cool World, and Simply Heavenly.

Stewart went on to land roles in various television series including That Girl, Marcus Welby, M.D., The Bob Newhart Show, Good Times, and Harry O. One of his most memorable roles was as Henry Jefferson, George Jefferson's brother, in the series All in the Family. In 1973, he co-starred in the short-lived series Roll Out. The following year, Stewart directed two episodes of another short-lived series Get Christie Love!, then co-starred in On the Rocks. After On the Rocks was canceled in 1976, Stewart portrayed the role of Marvin Decker in the Bewitched spin-off series Tabitha from 1977 to 1978.

On July 11, 1976, Stewart married Annie Dong. The couple had one child together, a daughter. On February 24, 2002, Mel Stewart died of Alzheimer's disease.

In the 1980s, Stewart starred on Scarecrow and Mrs. King as section chief Billy Mel Rose during the show's four-year run from 1983 through 1987, and continued guest starring in both television and films. His last on screen appearance came in the 1993 film Made in America, starring Whoopi Goldberg and Ted Danson.