Mary Fuller was born in Washington, D.C., to Nora Swing and attorney Miles Fuller, she spent her childhood on a farm. As a child, she was interested in music, writing and art. Her father died in 1902, and by 1906, she was working in the theater under the name Claire Fuller. She worked briefly with the Lyceum Stock Company in Toledo, Ohio. Mary Fuller began her acting career as a stage actress. At age 18 she was working in live theatre and in 1907 she signed with Vitagraph Studios in Brooklyn, NY, where she made films such as a one-reel adaptation of Elektra (released in April 1910). Later Fuller joined the Edison Film Company in 1910. That year, she appeared in the first film version of Frankenstein based on the Mary Shelley novel. Mary Fuller became a major early movie star who, by 1914, rivaled Mary Pickford in popularity. She appeared in a wide variety of roles, and starred in such melodramas as The Witch Girl, A Daughter of the Nile, The Active Life of Dolly of the Dailies (1914), and Under Southern Skies, her first feature-length production. Also, Fuller authored a number of screenplays, eight of which were made into films between 1913 and 1915. Mary Fuller’s career, however, was over by 1917. As quoted in Sally Dumaux’s King Baggot: A Biography and Filmography of the First King of the Movies, an August 18, 1917 article in Variety stated though Fuller was “one of the best drawing cards of the Universal for a long time … her last few pictures were both financial and productional disappointments … and at the expiration of her contract she was allowed to depart. … Miss Fuller has offered her services to several concerns along Broadway, but it is understood that they were turned down with the remark, ‘You are no longer [a] film type.'” Following this episode, Fuller disappeared from public view and her whereabouts remained a mystery for decades.

After the demise of the first stage of her film career, Mary Fuller apparently suffered a nervous breakdown following a failed affair with a married opera singer. She retired from the film business, and went to live in her mother’s home. In her early years, Mary Fuller had talked about a constant feeling of loneliness that film stardom never filled; however, in 1926, she returned to Hollywood and unsuccessfully attempted to resume her screen career. The death of her mother in 1940 brought a second nervous breakdown; after being cared for by her sister, on July 1, 1947, Mary Fuller was admitted to Washington’s St. Elizabeths Hospital, where she remained for 25 years. When Mary Fuller died, the hospital was unable to locate any relatives. She is buried in Congressional Cemetery.