Following the death of her first husband, Thomas Henry Watkins, Preston embarked on a career as an illustrator to support herself. She socialized and exhibited with artists of the Ashcan School and married one of the group, James Moore Preston, in 1903. They traveled to Europe together, summered on Long Island, and co-illustrated a magazine story. She became a successful illustrator for magazines, like "Harper's Bazaar" and "The Saturday Evening Post," and was a successful book illustrator. Considered one of the top women illustrators between 1900 and 1940, Preston was one of the few female members and exhibitors of the Society of Illustrators, having been admitted March 29, 1904 after peers Florence Scovel Shinn, Elizabeth Shippen Green, Violet Oakley, and Jessie Willcox Smith. Like them, she was only an Associate Member since full membership was not allowed for women until the 1920s. She exhibited at the 1913 Armory Show and won a medal at the Panama–Pacific Exposition in 1915. Preston was one of the major suffrage artists. Her works are in a number of museum collections. She played herself a chapter of the film serial "Our Mutual Girl" that was shown in theaters in 1915.