Her parents were Kenneth Perrine and Winifred McGinley; she grew in different places around the Northern Hemisphere, since her father was a military officer, and the family was moved to several different posts, as military families do. Perrine began her career as a Las Vegas showgirl. She made her motion picture debut with an uncredited part in Diamonds Are Forever (1971), and next she played the soft-core porn actress Montana Wildhack in Slaughterhouse-Five (1972). Her most prominent, world-famous movie role was as Miss Eve Teschmacher in Superman (1978) and in Superman II (1980).

Many people see a strong resemblance between Valerie and the famous Swiss actress Ursula Andress, who also appeared in Playboy as a "Bond Girl". Valerie was photographed as a model for a pictorial layout in the May 1972 issue of Playboy magazine, and she appeared on the cover of this magazine in August 1981.

In 1975, she was nominated for the Academy Award for the Best Actress in a Leading Role for playing Honey Bruce in Lenny (1974), for which she was also nominated for a Golden Globe for Best Motion Picture Actress - Drama. She was also nominated for the 1979 Saturn Award as Best Supporting Actress in Superman (1978).

She had further good roles playing Carlotta Monti in W. C. Fields and Me (1976) and Charlotta Steele in The Electric Horseman (1979), but her career grew bumpy when she appeared in such movies as Can't Stop the Music (1980), for which she was nominated for a Razzie Award for Worst Actress. In The Border, 1982, she played the role of Marcy, the wife of the corrupt police officer, Charlie, who was portrayed by Jack Nicholson. Since then she has worked steadily in lower-profile projects.