The University of Pennsylvania's School of Medicine, presently located in the University City section of Philadelphia, Pennsylvania, was the United States's first school of medicine, founded at the College of Philadelphia, as the University was then called. It is widely regarded as one of the nation's top medical schools, and in 2007, was ranked third overall among research-based medical schools by US News and World Report.

The school's young founder, John Morgan, was among the school's Edinburgh, Scotland educated faculty. In the autumn of 1765, students enrolled for "anatomical lectures" and a course on "the theory and practice of physick." Modelling the School after the University of Edinburgh, they emphasized the need for supplement medical lectures with bedside teaching, which they had made available to them at Pennsylvania Hospital by the practitioners there.

The School of Medicine's faculty was nationally renowned: Benjamin Rush (medicine), Philip Syng Physick (surgery), Robert Hare (chemistry) and, around the 1850's, William Pepper (medicine) and Joseph Leidy (anatomy). In 1847, the group of physicians who organized the American Medical Association effectively gave recognition to the School's fame by naming the AMA's first president Nathaniel Chapman, Professor of Medicine at the School.

In the 1870's, the School of Medicine's faculty persuaded the University's trustees to build a teaching hospital along with the newly moved campus, from downtown Philadelphia to its current location just west of the Schuylkill River. At the Hospital, the faculty of the School played an integral part in promoting and implementing an important aspect of the Flexner Report of 1910: to have a bedside teaching program specifically conducted by appointed clinical faculty. During the late nineteenth and early twentieth centuries, the School of Medicine was one of the earliest to encourage the development of the emerging medical specialties: neurosurgery, ophthalmology, dermatology, and radiology. Between 1910 and 1939, the chairman of the Department of Pharmacology, Alfred Newton Richards, played a significant role in developing the University as an authority of medical science, helping the United States to catch up with European medicine and begin to make significant advances in biomedical science.

In 1993 the Hospital (or Medical Center including the School of Medicine), was included in the University of Pennsylvania Health System, the University's response to the changing national climate of health care. The Health System includes a clinical care network in which the professional associates of the Health System provide hands-on teaching for students of the School. This arrangement allows the faculty to address changes in health care delivery in an educational environment. Currently, the University uses the umbrella organization Penn Medicine to administer and coordinate the School of Medicine and the Health System.

Benchmark changes in the understanding of medical science and the practice of medicine have necessitated that the School change its methods of teaching, as well as its curriculum. Large changes were made in 1968, 1970, 1981, 1987, and 1997. The last significant change in 1997 brought about the institution of Curriculum 2000®, "an integrated, multidisciplinary curriculum which emphasizes small group instruction, self directed learning and flexibility." http://www.med.upenn.edu/history.html Three themes, Science of Medicine, Art and Practice of Medicine, and Professionalism and Humanism, were developed by focus groups consisting of department chairpersons, course directors, and students.