In 1973, to improve health care for citizens in South Carolina, the South Carolina Commission on Higher Education and the State Legislature authorized the University of South Carolina to apply for a grant from the Veterans Administration to assist in the development of the medical school.  The grant, funded through the Teague-Cranston Act, was approved in 1974.  Faculty recruitment and curriculum planning began in 1975; in 1976, the University of South Carolina School of Medicine received provisional accreditation from the Liaison Committee on Medical Education (LCME) of the American Medical Association and the Association of American Medical Colleges. 

In the fall of 1977, the USC School of Medical admitted its first class of 24 medical students.  The charter class graduated May 1981, at which time the School of Medicine was fully accredited by the LCME. In 1991, the School of Medicine's affiliation with the Greenville Hospital System was enhanced to provide the opportunity for completion of core third- and fourth-year clerkships and rotations at that facility for students interested in completing their medical educations in upstate South Carolina.
Medical student class size has tripled since the entrance of the first class, and approximately 300 medical students are enrolled in the four-year program.

The School of Medicine’s educational programs were further augmented with the establishment of additional graduate programs:

• Ph.D. Program in Biomedical Sciences—1981
• M.S. Program in Genetic Counseling—1985
• M.S. Nurse Anesthesia—1994
• M.S. Program in Rehabilitation Counseling—1994
• M.S. Program in Biomedical Sciences—1998