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.

[11][12] In 2021 UF Health acquired Scripps Research's Florida branch in Jupiter, FL.

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

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.