Hergesheimer was a student at the Girls High School in Reading, Pennsylvania, where her art teacher encouraged her to make a career of art. She went on to attend the Pennsylvania Academy of the Fine Arts, studying under William Merritt Chase and Cecilia Beaux. Hergesheimer was the great, great granddaughter of Charles Willson Peale, one of the pre-eminent American artists of the early years of the nation. Peale was well known for naming many of his children after European Renaissance artists including Titian, Rembrandt, and Raphaelle. Hergesheimer's parents were aware of this tradition, and her middle name is that of one of the Italian artists, Sofonisba Anguissola.
