In the early 1800s, only four colleges in the United States had medical schools affiliated with them, namely Columbia, University of Pennsylvania, Harvard and Dartmouth. For many years, Penn alumni blocked all efforts to create an additional medical school in Philadelphia. Dr. George McClelland and associates devised a plan to bypass this situation. In 1824, McClelland petitioned Jefferson College at Canonsberg (now Washington and Jefferson College) to add a medical school to their institution. While technically part of Jefferson College in western Pennsylvania, Jefferson Medical College was to be located in Philadelphia under the direction of the medical faculty. Although the University of Pennsylvania challenged this action, in 1826, the state legislature passed a bill that ratified the actions of Jefferson College in establishing the medical school. This allowed Jefferson Medical College to grant medical degrees. By 1838, Jefferson Medical College gained its own charter and was no longer affiliated with Jefferson College. As a proprietary school, the faculty administrated and managed all the finances of the school. This included the sale of “tickets” to attend lectures.

An infirmary to treat the poor was established in 1825. The establishment of this dispensary to treat indigent patients under student observation was the first instituted by any medical school in the United States. Eventually, all medical schools in the United States adopted Jefferson's example of combining lectures with practical patient experience. In 1828, the Ely building provided space for a lecture hall and an amphitheatre, also known as the “pit,” for operations.