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Francis H. Appleton was born on 17 June 1847 to a family heavily involved in government, both of his grandfathers having been members of Congress. Appleton attended preparatory schools and studied with a private tutor in order to prepare him for college. He graduated from Harvard in 1869 and went on to attend the Massachusetts Institute of Technology, but remained there for only a short time. After leaving M.I.T. Appleton decided that he would try his hand at farming, a decision made largely in hopes of improving his poor health by means of fresh air.

In 1871 Harvard opened the Agricultural Department, and so, desiring formal training in his latest pursuit, Appleton enrolled as a student in the Bussey Institute. While studying at the Bussey Institute, he also bought an estate in Peabody where he was able to put his training to practical use. Appleton chose farming as his primary occupation, although he had financial interests in many other enterprises and managed his investments by himself. He served as director, president, trustee, secretary, librarian, etc. for countless institutions and also held memberships at an astounding number of clubs.