The first hospital in Waycross was built in 1876 for employees of Plant Railroad System. It was later operated by Atlantic Coast Railroad. In 1907, supported by community funds raised from personal donations, oyster suppers and bazaars, construction was completed and King's Daughters Hospital opened to the general public on Brunel Street. Sadly, a fire at the King's Daughter's Hospital moved the operation to Williams Street in 1928. A bond referendum of $150,000 laid the ground for a new 60-bed facility. The new facility, Ware County Hospital, opened on State Street in 1929.
After World War II, the Waycross economy was in a state of growth and rebirth when the county's hospital was built on Darling Avenue in 1956. The new hospital, Memorial Hospital of Waycross, expanded over the course of the next 30 years as major construction projects added patient care units. In 1987, Satilla Health Services, Inc., a non-profit corporation was formed to support growth beyond the boundaries of Ware County. Satilla leased and assumed control of Memorial Hospital.
In 1991, Memorial Hospital changed its name to Satilla Regional Medical Center to reflect its regional status and patient base. A year later, a $7.4 million construction project added 47,250 square feet of space to the hospital, which included a new lobby, admissions, radiology, and emergency departments. The hospital facility expanded once again in 2001 with the addition of a new main entrance, surgical services, cardiac diagnostic services, intensive care and coronary care units, and labor and delivery services.
In 2010, Satilla Regional Medical Center broke ground on a three-story, 25,000 square foot expansion project that added a 16-bed Progressive Cardiac Care Unit, as well as additional space for surgical support.
In March 2012, leaders from Satilla Regional Medical Center and Mayo Clinic in Florida signed an agreement to integrate Satilla into Mayo Clinic, making Satilla the first Mayo Clinic Health System location in Georgia. On May 1, 2012, Satilla Regional Medical Center began using its new name: Mayo Clinic Health System in Waycross.