Before 1920, the black population of St. Louis was not permitted inside the walls of the public City Hospital, even though their numbers had increased by 60% over the past decade. In response, leaders of the black community purchased a 177 bed hospital for use in 1919, named City Hospital #2. This facility was still inadequate, however, to treat the 70,000 black residents of St. Louis.

A local black attorney named Homer G. Phillips led a city-wide campaign to build a larger black hospital.  Although a bond issue was passed in 1923, it would be nine years later — and after the murder of Homer G. Phillips — before construction of the new hospital would begin.

The main hospital buildings were completed between 1933 and 1935, and the ancillary wings between 1936 and 1937. At the dedication ceremony on February 22, 1937, Secretary of Interior Harold L. Ickes told the community the new hospital would help them “achieve [their] rightful place in our economic system.”  In 1942, the hospital was renamed in honor of Homer G. Phillips.

By 1948, the resident physicians at the hospital included more than a third of the graduates from the only two black medical schools in the nation. In addition to schools for nursing, x-ray technicians, laboratory technicians and medical records staff, the hospital also allowed foreign doctors to train at the facility. The hospital also led the nation in developing treatments for gunshot wounds, ulcers, and burns.

In 1955 the City of St. Louis was ordered to desegregate its hospitals. Although the Hospital complied, it still remained mostly black in staff and patients. As early as 1961, the City started to discuss a merger between Homer G. Phillips and City Hospital. By the end of the decade, many of the services at Homer G. Phillips were reduced or eliminated altogether.

The merger efforts stalled for another decade.  On August 17, 1979, St. Louis closed all inpatient services at the hospital. This resulted in local protests and forced the police department to escort the remaining patients from the hospital. Even though a task force was charged with finding the reasons for the hospital closure, little results and the hospital did not reopen.  By 1985, and with a listing on the National Register of Historic Places, the hospital facility was closed completely.