Flood was born in Jamaica, New York. She enjoyed notable roles on Broadway, making her debut in 1954's Kismet and going on to play opposite Don Ameche in 1957's Holiday for Lovers. Her television debut came earlier, in a 1952 live production of the W. S. Gilbert play, The Fortune Hunter, for WOR-TV.
She became a regular performer on golden age live TV shows, including Sergeant Bilko, Armstrong Circle Theatre, Kraft Theatre, and The Philco Television Playhouse. She was also known for roles in various commercials, including those for Good Seasons salad dressing. Before starting on The Edge of Night, she played the leading role of another journalist, Elizabeth "Liz" Fraser Allen in the short-lived soap opera From These Roots from 1958-61.
In The Edge of Night, Nancy's marriage to Mike Karr remains as one of the longest in soap history. Nancy and Mike had no children of their own, but the character of Laurie (Mike's daughter by his first wife Sara) came to consider Nancy as her mother. Flood continued in the role through the series' finale in 1984, by which time she was the show's longest-serving cast member.
After Edge of Night, Flood continued to act in daytime dramas. She was cast in a succession of shorter-term and recurring roles, playing Ella Hobbs, a villain on Search for Tomorrow, who tried to kill the show's leading character, Joanne, and played a variety of society matrons on Another World (Rose Livingston, 1986-1987), One Life to Live (Mrs. Guthrie, 1991), and As the World Turns, recurring from 1992-1993 as business executive Ruth Mansfield. In 1987, she joined the cast of All My Children playing the recurring role of Bitsy Davidson, Cecily's snooty mother, and was briefly under contract to the show. Her last appearance aired in January 1990. Other work included guest-starring roles in prime-time TV programs such as The Cosby Show, and a role in the 1988 feature film, Mystic Pizza.