In New York in the early 1940s Mary's early interest in art led her to courses at the Art Students League where she worked with painters such as George Grosz. She lived mainly in New York but spent time in Washington where she studied with Eugene Weiss from the Corcoran Museum School. In the early 1940's Mary also worked as a model and appeared on the covers of Vogue and Harper's Bazaar, among others. In 1948, she met the sculptor David Hare, who introduced her to an experimental school called The Subject of the Artist. Through these associations Abbott moved into the heart of the New York avant-garde. In the early 1950's Mary spent time with her second husband Tom Clyde in the Virgin Islands, where she produced a great deal of work. The two then moved to Southampton, New York where Mary still resides.

Back in New York City, Mary became a member of the Artist's Club, where she was one of three female members along with Perle Fine and Elaine de Kooning. Also in the early 1950's Mary began to exhibit extensively with shows at Kootz, Tibor de Nagy and Tanager. She was also in three of the famous Stable Gallery Annuals.

In the 1970s Abbott taught at the University of Minnesota in Minneapolis but eventually returned to New York where she continues to maintain homes in both the city and in the Hamptons. Mary has often said that her life's work is to "define the poetry of living space," something she has been doing for over sixty years.