Named after its benefactor, Bowman Gray School of Medicine opened in Winston-Salem in 1941, affiliating with N.C. Baptist Hospital to create "The Miracle on Hawthorne Hill".

In 2011, as part of the institution's move to become a unified structure, the corporate entity was rebranded as Wake Forest Baptist Medical Center.

[3] In 2002, Wake Forest Baptist began operating the Davie County Hospital in Mocksville, which was built in 1956 and expanded in 1965 and 1974.

In July 2017, Wake Forest Baptist began a 30-year lease with Wilkes Medical Center after an agreement with North Wilkesboro.

On April 10, 2019, Wake Forest Baptist and Atrium Health in Charlotte, North Carolina, signed a memorandum of understanding as the first step toward a partnership.

[12] More specific details about the medical school were revealed in February 2021, including plans for a seven-story tower, and on March 24, 2021, Atrium Health announced a 20-acre site at Baxter and McDowell streets.

Key tenants in the park are the Wake Forest Institute for Regenerative Medicine (WFIRM), which is working to engineer replacement tissues and organs and develop healing cell therapies for more than 40 different areas of the body, and Inmar, an information technology company that employs 900 people.

[17][18] Wake Forest Baptist Health also operates a network of subsidiaries and affiliate hospitals, including Wake Forest Baptist Health–Lexington Medical Center, a 94-bed acute-care facility in Lexington, NC, and Wake Forest Baptist Health–Davie Medical Center, which includes a 25-bed inpatient hospital in Mocksville, NC, and an outpatient campus in Bermuda Run, N.C., featuring a 24/7 emergency department, imaging and diagnostic services, and various specialty health and medical offices.

[20] The medical center was ranked for 2015–16 by U.S. News & World Report as among the nation's best hospitals in seven areas: Cancer, Ear, Nose & Throat, Gastroenterology & GI Surgery, Nephrology, Neurology & Neurosurgery, Pulmonology, and Urology.

It is ranked as high-performing in five additional adult specialties: Cardiology and Heart Surgery, Diabetes and Endocrinology, Geriatrics, Gynecology, and Orthopedics.

[23] The Childress Institute, located at Wake Forest Innovation Quarter, is focused on funding research and medical education throughout the U.S. to improve treatment, as well as raising public awareness about the magnitude of pediatric trauma.