Born in California in 1875, Watkins began her artistic training at the Art Students League in New York, where her father, James T. Watkins, had moved the family in 1890 to work as an editorialist for the New York Sun. Encouraged by her wealthy, well-connected parents, Watkins took classes at the League between 1893 and 1896, when Chase, Kenyon Cox, and other prominent American painters served on its faculty. In 1896, shortly after her father's death, she and her mother, Susan Ella Owens Watkins, departed for Paris, where they would remain for the next fourteen years. In Paris Watkins continued her studies with the painter Raphael Collin. A disciple of William Bouguereau and Alexandre Cabanel, Collin provided the young American with a solid grounding in the French academic style. He also urged his pupils to sketch outdoors, an activity that surely helped to prepare Watkins for her later plein-air studies of Parisian scenes.

By 1912, Watkins had fallen ill, most likely from cancer. Her health failing, she at last consented to marry her longtime suitor, Goldsborough Serpell, and moved with him to Norfolk. In little more than a year after their marriage, she was admitted to Baltimore's Johns Hopkins Hospital, where she died in June 1913. She was thirty-seven years old.

At his death in 1946, Norfolk, Virginia, banker Goldsborough Serpell bequeathed to the Norfolk Museum of Arts and Sciences a remarkable gift of paintings, oil studies, academic drawings, and sketches by his wife, the artist Susan Watkins. Among the most important acquisitions made by the museum prior to the arrival of Walter P. Chrysler's collection in 1971, the donation comprises sixty-two works of art by Watkins, as well as photographs, scrapbooks, and other memorabilia documenting her career. It also includes a posthumous portrait of the artist painted by her colleague and longtime friend William Merritt Chase. The Serpell bequest constitutes a veritable life's work, a rich artistic archive through which the Chrysler can tell the story of Watkins's exceptional, and tragically brief, career.