From 1894 to 1899, Claypole served as a professor of physiology and histology at Wellesley College, and also headed the zoology department for two years.

In 1899, she started work in the medical department at Cornell where she stayed until 1901 when she moved to Pasadena to be near her stepmother, who was ill.

[1] On a request from William Osler, Claypole was working on an immunization for typhoid (needed for the armies of World War I).

Although she had been vaccinated, her work continuously exposed her to the pathogen, and she eventually succumbed to the disease when it caused a perforated intestine,[1] along with appendicitis.

[2][4][5] In her honor, the University of California set up the Edith Claypole Memorial Research Fund in Pathology.