She has appeared in a number of motion pictures as well as on television including Caesar's Hour, One Day at a Time, The Carol Burnett Show and Coach among others. She also had a recurring role on The Mary Tyler Moore Show as Mary's mother, and is a winner of three Emmy Awards.

Originally named Fabares, she is the aunt of actress/singer Shelley Fabares. Nanette Fabares changed her name to a phonetic spelling after it was mispronounced as "Fa-bare-ass" by Ed Sullivan. (She told this story in a live performance 8 December 2004).

Fabray's official biography has at times stated that she appeared in Our Gang shorts at the age of seven, although she never appeared in the series.

One of her most memorable film appearances was in the musical, The Band Wagon (1953) opposite Fred Astaire and Cyd Charisse. She and Oscar Levant played a team of scatterbrained screenwriters who try to help a fallen star (Astaire) make his comeback.

Nanette Fabray overcame significant hearing impairment to pursue her career. She is also an advocate for the hearing-impaired. Some comedians, over the years, have suggested that entertainer Michael Jackson has surgically altered his face using Fabray, with her finely chiseled nose, high cheeks and wide eyes, as his model.

Nanette Fabray has a star on the Hollywood Walk of Fame.

She was married to screenwriter and director Ranald MacDougall (1957-1973).