Russell was raised in Atlanta, where he began performing as a child in a singing and dancing troupe. He served in the army as a medic during World War II and later returned to college to finish a degree in English at the University of Cincinnati in 1946. After touring comedy clubs in the the Midwest, Russell moved to New York, where he attracted attention for his nightclub comedy performances. He cultivated a persona distinct from those of other comedians of the 1950s, eschewing the increasing vulgarity then popular in favour of sharply observed social commentary and elaborate wordplay. As the burgeoning civil rights movement gathered strength in the 1960s, Russell more frequently incorporated material about racism into his onstage commentary.

Russell's rhymes, witty one-liners, and sophisticated topical jokes gained him a number of guest stints on talk and game shows, notably The Tonight Show in 1959. In 1964 he became the first African American to join a network game show as a regular panelist when he began appearing on Missing Links. Other TV game shows on which he made frequent appearances included Hollywood Squares, To Tell the Truth, and The $50,000 Pyramid. As an actor, Russell included among his credits the roles of Officer Anderson on the TV series Car 54, Where Are You? (1961–62) and the Tin Man in the film The Wiz (1978).