St. Louis Medical College was chartered in 1841 as the medical department of St. Louis University. The university appointed the first faculty, but allowed them to be governed by an autonomous, nonsectarian Board of Trustees. Instruction began in October 1842 in a small building that was owned by the first dean, James Vance Prather, located on Washington Avenue near Tenth Street and adjacent to the university buildings. In 1849 the college moved to a neoclassical style building at Clark Avenue and Seventh Street built by the financier John O'Fallon. Despite the nonsectarian board, public pressure -- particularly from the extreme nativist movement, the so-called "Know Nothing" party -- demanded that the department sever ties with the Roman Catholic university. In 1855, the state of Missouri granted the college a charter as an independent institution.
In the 1850s and 1860s St. Louis Medical College was so dominated by one man, the second dean, Charles Alexander Pope that it was commonly referred to as "Pope's College." There was some literal truth to the name, because Pope owned the Seventh Street building outright. On Pope's death in 1870, his colleagues were forced as a group to raise funds to buy the facility. That group organized under the name of the Medical Fund Society of St. Louis.
In the 1870s the curriculum of the college was reformed and expanded. By 1880, all students were required to matriculate for three years before receiving a diploma. In 1891, St. Louis Medical College became affiliated with Washington University and was designated its medical department. For eight more years, however, the old name was maintained, and the medical school was known jointly as the Washington University Medical Department and Saint Louis Medical College. This dual name was dropped only when the Missouri Medical College affiliated with the university in 1899.
In 1892 the Medical Fund Society and Washington University sponsored the construction of a new facility at 1804 Locust Street. The building was praised for being "commodious and well planned." But less than twenty years later, the same building was devastatingly criticized by Abraham Flexner in his famous report to the Carnegie Commission. With the reorganization of Washington University School of Medicine in 1910, most of the remaining traditions of St. Louis Medical College were abandoned in the interests of progressive medical education.