Vestoff was born into a family of vaudeville performers in New York City. Both her Russian immigrant father and mother, who was the great niece of American composer Stephen Foster, died and left Virginia an orphan at the age of nine. She coped with the loss by acting, and took third prize on The Ted Mack Amateur Hour, which launched a professional career with the Children's Chorus of the New York City Opera.
While living with relatives, Virginia attended the New York High School for the Performing Arts. At 15, she decided to move out and manage life on her own by attending Washington Irving High School and moonlighting as a salesgirl at a department store. However, Virginia quit school early to tour with a dance company. The failure to graduate remained a personal regret to Virginia throughout her life, which she countered with a thirst to self-educate, becoming an extensive reader.
Soon after dropping out, Vestoff landed a part on stage in The Boyfriend and it led to many of her other theatrical credits including I'm Getting My Act Together and Taking It On the Road, Spokesong, Drinks Before Dinner, The Misanthrope, Love and Let Love, Man With a Load of Mischief, Ben Bagley's New Cole Porter Revue, And in this Corner, A Doll's House, Fallout, The Crystal Heart, Private Lives, The Threepenny Opera, The Archbishop's Ceiling, Booth is Back in Town, Camelot, Put it in Writing, The King and I, and My Fair Lady.
Vestoff made her Broadway debut in the 1960 revue From A to Z. Her most famous stage role was that of Abigail Adams in 1776, a role she reprised in the motion picture adaptation. Additional Broadway credits include Irma La Douce, Boccaccio, Via Galactica, and Baker Street, in which she met her future husband, writer Morty Lefkoe.
For a time, Vestoff took on dual duties with Broadway and daytime drama. From 1969 to 1970, she filled in for Elizabeth Hubbard as Dr. Althea Davis on The Doctors and then later joined the cast of Dark Shadows as Samantha Collins.
Vestoff also did another soap opera stint on As the World Turns and appeared in numerous television commercials, including Sure Deodorant, Geritol, Hamburger Helper, Sardo Bath Beads, and Bradlees.
Vestoff's primetime television guest credits included The Quinns, Carmody, Contact: The Case of the Secret Message, We Interrupt This Season, Alone at Last and Kojak. Her big screen roles included Robert Altman's A Wedding and Such Good Friends.
Vestoff succumbed to cancer in New York City at age 42.
