Shands was recruited to the effort to create a teaching hospital in the Gainesville area, though he at first considered that a larger city might be a better site, and was instrumental in obtaining state funding.

In 1969, the UF College of Medicine established a satellite campus in Jacksonville at Duval Medical Center; this was renamed University Hospital in 1971.

[5] The UF network purchased Alachua General Hospital in east Gainesville from Santa Fe Health Care in 1996, changing the name to Shands AGH.

[9] The system simultaneously opened a cancer hospital south of its main location on the UF campus.

The following tertiary facilities represent the core of UF Health's academic, teaching, trauma, specialty and research-related hospitals.

A new hotel for family and outpatients is also being constructed immediately south of the Cancer and Neuromedicine buildings.

In 2020 UF Health acquired two new hospitals, Leesburg Regional Medical Center and The Villages® Regional Hospital [12][11][16] UF Health announced in February 2023 that it intended to acquire Flagler Health+ in St. Johns County, and formally completed the acquisition in September 2023.

In 2022 UF Health announced a partnership with Jupiter Medical Center, and plans to jointly open a hospital in Palm Beach Gardens, FL.