Her mother was French and her father was Vietnamese; French is Nuyen's first language and she speaks no Asian languages. During the Second World War, her mother and grandfather were persecuted by the Nazis for being Gypsies. She was raised in Marseille by a cousin, whom she describes as "an orchid raiser who was the only person who gave a damn about me."

She became a stage actress and portrayed Suzie Wong in the theatrical production of The World of Suzie Wong in 1958, opposite William Shatner whom she later worked with again in an episode of Star Trek (as the memorable Elaan of Troyius). She was about to portray Suzie Wong in the film production but was replaced by Nancy Kwan.

She then went on to appear in Television and film including South Pacific (1958), Battle for the Planet of the Apes (1973), and The Joy Luck Club (1993). She met her second husband, Robert Culp, while appearing on his TV show I Spy; they married in 1967 but divorced in 1970. In 1986, she earned a master's degree in Clinical Psychology and began a second career as a psychological counselor for abused women and children, and women in prison. She received a "Woman of the Year" award in 1989 for her psychological work.

From 1963 to 1966, she was married to Dr. Thomas Gaspar Morell, with whom she has a daughter named Fleur (who is happily married and resides in Canada).