Price was born in St. Louis, Missouri to Vincent Leonard Price and Marguerite Willcox. His father was president of the National Candy Company. His grandfather, Vincent Clarence Price invented "Dr. Price's Baking Powder", the first cream of tartar baking powder, and secured the family's fortune. Vincent Jr. attended St. Louis Country Day School. He was further educated at Yale in art history and fine art. He was a member of Alpha Sigma Phi Fraternity and the Courtauld Institute, London. He became interested in theater in the 1930s, appearing professionally on stage from 1935.
He made his film debut in 1938 with Service de Luxe and established himself as a competent actor, notably in Laura (1944), opposite Gene Tierney, directed by Otto Preminger. He also played Joseph Smith, Jr. in the movie Brigham Young (1940). During the 1940s, he appeared in a wide variety of films from straight-forward drama to comedy to horror (he provided the voice of The Invisible Man at the end of Abbott and Costello Meet Frankenstein in 1948). In 1946 he reunited with Gene Tierney in two notable films Dragonwyck and Leave Her to Heaven. He was also active in radio, portraying the Robin Hood-inspired crime-fighter Simon Templar, aka. The Saint, in a series that ran from 1947 to 1951.
In the 1960s, he had a number of low-budget successes with Roger Corman and American International Pictures (AIP) including the Edgar Allan Poe adaptations House of Usher (1960), The Pit and the Pendulum (1961), Tales of Terror (1962), The Raven (1963)
Price was married three times and fathered a son, named Vincent Barrett Price, with his first wife, former actress Edith Barrett. Price and his second wife Mary Grant donated hundreds of works of art and a large amount of money to East Los Angeles College in the early 1960s in order to endow the Vincent and Mary Price Gallery there.
Price's last marriage was to the Australian actress Coral Browne, who appeared with him (as one of his victims) in Theatre of Blood (1973). He converted to Catholicism to marry her, and she became a US citizen for him.