In 1959, Virginia Dwan opened her first gallery on 1091 Broxton Avenue in the Westwood Village neighborhood of Los Angeles, California. Her independent wealth allowed her to open a gallery without worrying about business and sales. Three years after opening, the Dwan Gallery moved into a new Westwood Village space especially designed to express the gallery's contemporary aesthetic. In 1965, Virginia Dwan moved to New York City and founded an east coast branch of the Dwan Gallery at 29 West 57th Street.
Early exhibitions at the Dwan Gallery showed Abstract Expressionist artists and works of art from New York which Dwan consigned from other galleries. After traveling to New York and France, Virginia Dwan's interests and tastes manifested in exhibitions by 1961 with Yves Klein. Through Klein, Dwan made connections to other Nouveaux Réalistes artists that the gallery featured in solo and group shows. Later exhibitions featured Land and Minimilist artists. Dwan recognized that many of her shows were not considered salable but continued to show the avant-garde. She saw the gallery as an opportunity to expose the public to different styles of art.
Virginia Dwan maintained a close and personal relationship with many of her artists. She allowed large stipends to gallery artists and invited them to spend time at her home in Malibu, California. When working with artists concentrating on found objects, Dwan would accompany them on scavenger hunts and shopping trips. In the case of Robert Smithson and other Land Art artists, she traveled to offsite locations to visit works of art in progress. Dwan relied on her longtime gallery director, John Weber to interact with collectors as she preferred to maintain her connection with the artists.
The Dwan Gallery Los Angeles closed in mid-1967 but the New York branch remained open. By 1971, Virginia Dwan felt pressure to support her thirteen artists through a period of economic insecurity. She decided to close the gallery secretly and only informed her artists at the last minute. The final exhibition at Dwan Gallery New York closed in June of 1971.