The Medical College of South Carolina was one of the first medical schools in the United States to establish, in 1834, an infirmary specifically for teaching purposes. In the 1840s the college also entered into agreements for clinical training opportunities at the Poorhouse, the Marine Hospital, and the local "dispensary." In 1856, Roper Hospital was opened, and for 100 years Roper was the Medical College's primary teaching hospital.

The Medical College recognized the need for its own facilities to expand clinical teaching opportunities, as well as to serve as a major referral center in South Carolina for diagnosis and treatment of disease. The ten-story Medical University Hospital accepted its first patients in 1955. In 1985 the name of the hospital and its clinics was changed to MUSC Medical Center, reflecting its function in an academic health institution and its wide range of services to the public. This comprehensive facility is now comprised of three separate hospitals (the University Hospital, the Institute of Psychiatry, and the Children's Hospital). The Medical Center includes centers for specialized care (Heart Center, Transplantation Center, Hollings Cancer Center, Digestive Diseases Center). Numerous outpatient facilities include the Family Medicine Center, University Diagnostic Center, and affiliated faculty practice association ambulatory care centers. In the past ten years, $200 million in capital improvements for the Medical Center focused resources on improved quality of patient care and accessibility of services. In 1993-94 there were over 23,000 inpatient admissions and almost 300,000 outpatient visits. MUSC also manages the Charleston Memorial Hospital adjacent to the campus, providing there a low-risk obstetrical service.

Among the programs which have earned distinguished reputations at the Medical University of South Carolina are: neuroscience, substance abuse, cardiovascular medicine, drug sciences, perinatal medicine, burn care, ophthalmology, hearing loss, genetics, rheumatology, and cancer care.