The West Virginia School of Osteopathic Medicine, located in Lewisburg, was chartered in December 1972 as the Greenbrier College of Osteopathic Medicine. It was housed in buildings that had been vacated by the Greenbrier Military School. The new school was founded by a small group of West Virginia osteopathic physicians who felt a need for a medical school to train primary care physicians for rural West Virginia.

Osteopathic medicine was founded in the 1870s by A. T. Still, M.D., as a response to the often ineffective and sometimes harmful medical practices of the time. Still felt that all parts of the body were interrelated and that the body should be treated as a whole. He opened the first osteopathic school of medicine in Kirksville, Missouri, in 1892. Osteopathic physicians began practicing medicine in West Virginia in the first decade of the 20th century. Osteopathic physicians are fully educated in all areas of conventional medicine, and they also receive specialized training in the manipulation of the body's musculoskeletal system to treat certain medical conditions. They may choose to specialize in any area of medicine, but a large proportion of them become primary care physicians. Upon completion of four years of osteopathic medical school, students receive the D.O. (Doctor of Osteopathy) degree.

Initial funding for the Greenbrier College of Osteopathic Medicine came from the Appalachian Regional Commission, the West Virginia legislature, and the U.S. Department of Health, Education and Welfare. Private osteopathic physicians in West Virginia also provided loans and contributions. The school opened its doors to students on October 14, 1974, with accreditation by the American Osteopathic Association. On March 6, 1975, Governor Arch Moore signed a bill that brought the school into the state's system of higher education as the West Virginia School of Osteopathic Medicine. The first class of 33 students graduated in 1978.

In 1984, the School of Osteopathic Medicine started a postdoctoral training program in cooperation with area hospitals. A building program in the 1990s resulted in improved and expanded school facilities with the addition of a new library, clinic, science building, and alumni center. In recent years, the school has been consistently ranked by the magazine U.S. News & World Report as one of the top 50 medical schools in the United States for the training of primary care physicians.

The school has experienced rapid growth, from 362 in 2005 to 819 in fall 2015. By 2023-24, enrollment had remained relatively steady at 797. The 21st century increase in enrollment can be attributed, in part, to the growth of the non-resident student population.

West Virginia School of Osteopathic Medicine website