She began studying piano when she was eight, and the music of jazz greats such as Louis Armstrong and Duke Ellington filled her home.

[5] In her late teens and early twenties, McRae played piano at Minton's Playhouse, sang as a chorus girl, and worked as a secretary.

[8][9] Among her most interesting recording projects were Mad About The Man (1957) with composer Noël Coward, Boy Meets Girl (1957) with Sammy Davis Jr., participating in Dave Brubeck's The Real Ambassadors (1961) with Louis Armstrong, a tribute album You're Lookin' at Me (A Collection of Nat King Cole Songs) (1983), cutting an album of live duets with Betty Carter, The Carmen McRae-Betty Carter Duets (1987), being accompanied by Dave Brubeck and George Shearing, and closing her career with tributes to Thelonious Monk, Carmen Sings Monk (1990), and Sarah Vaughan, Sarah: Dedicated to You (1991).

As a result of her early friendship with Billie Holiday, she never performed without singing at least one song associated with "Lady Day", and she recorded an album in 1983 in her honor entitled For Lady Day, which was released in 1995, with songs including "Good Morning Heartache", "Them There Eyes", "Lover Man", "God Bless the Child" and "Don't Explain".

McRae also recorded with some of the world's best jazz musicians in albums such as Take Five Live (1961) with Dave Brubeck, Two for the Road (1980) with George Shearing, and Heat Wave (1982) with Cal Tjader.

[9] She withdrew from public performance in May 1991 after an episode of respiratory failure only hours after she completed an engagement at the Blue Note jazz club in New York.