Uggams gained wider recognition for portraying Kizzy Reynolds in the television miniseries Roots (1977), earning Golden Globe and Emmy Award nominations for her performance.

Uggams came to be recognized by TV audiences as an upcoming teen talent in 1958 on the musical quiz show series Name That Tune.

[9] Her records "One More Sunrise" (an English-language cover of Ivo Robic's "Morgen", 1959) and "House Built on Sand" made Billboard magazine's charts.

She also made guest appearances on such television programs as Family Guy (as herself), I Spy, Hollywood Squares, The Muppet Show, The Love Boat and Magnum, P.I..

In Inherit the Wind (1960), she sang the opening, "(Gimme Dat) Old Time Religion", and the closing, "Battle Hymn of the Republic".

Her film career includes roles in Skyjacked (1972), Black Girl (1972) and Poor Pretty Eddie (1975), in which she played a popular singer who, upon being stranded in the deep South, is abused and humiliated by the perverse denizens of a backwoods town.

[14] In April 2016, she portrayed Leah Walker, the bipolar mother of Lucious Lyon in the hit Fox series Empire.

Uggams appeared as Sadie in the 2017 television film The Immortal Life of Henrietta Lacks, and in 2018, she returned as Blind Al in Deadpool 2.

In 2023, Uggams voiced a character, Grandma, in My Dad the Bounty Hunter[17] and appeared as Agnes in the film American Fiction.

[21] Uggams replaced Patti LuPone as Reno Sweeney in the Lincoln Center revival of Cole Porter's musical Anything Goes on Broadway in March 1989.

[26] In January 2009, Uggams played Lena Horne in a production of the stage musical Stormy Weather at the Pasadena Playhouse in California, directed by Michael Bush and choreographed by Randy Skinner.