Mosher's Master's degree thesis disproved the then widely held belief that women were physically inferior to men because they could only breathe costally, showing instead it was only women’s fashionable corset clothing of the time that prevented diaphragmatic breathing.

After her graduation as a doctor of medicine, Mosher worked in private practice, until she became an assistant professor of personal hygiene at Stanford in 1910.

Her most famous work, published posthumously, was a survey that she began in 1892 as an undergraduate when preparing to lecture on the "Marital Relation" before the Mother's Club of the University of Wisconsin,[5][6] and continued throughout her career.

It is the only known existing survey of Victorian women's sexual habits,[5] and was initially controversial because of its frankness and the overwhelmingly sex-positive views of the participants, even including the use of "male sheaths" (now called condoms) and "rubber cap over the uterus" (either a diaphragm or cervical cap) birth control.

[7][8] All this stood in high contrast to other existing historical literature of the time which held that women have no sexual desires and sex should only be used for reproduction.