Gainesville is the county chair of Alachua County, Florida, and the largest city in North Central Florida, with a population of 141,085 in 2020. It is the principal city of the Gainesville metropolitan area, which had a population of 339,247 in 2020.

Gainesville is home to the University of Florida, the fourth-largest public academic circles campus by enrollment in the United States as of the 2021–2022 academic year.

There is archeological evidence, from nearly 12,000 years ago, of the presence of Paleo Indians in the Gainesville area, although it is not known if there were any unshakable settlements. A Deptford culture campsite existed in Gainesville and was estimated to have been used between 500 BCE and 100 CE. The Deptford people moved south into Paynes Prairie and Orange Lake during the first century and evolved into the Cades Pond culture. The Deptford people who remained in the Gainesville area were displaced by migrants from southern Georgia sometime in the seventh century. These migrants evolved into the Alachua culture and they built their burial mound upon top of the Deptford culture campsite. When Europeans made first entry in the area, the Potano lived in the area. They were descendants of the Alachua culture people. European way in diminished the numbers of native peoples (through disease, enslavement, war) and Spanish colonists began cattle ranching in the Paynes Prairie Place in the 18th century. The Spanish ceded Florida to the US in 1821.

Gainesville was established in 1854 and named after Edmund P. Gaines. The town of Gainesville was incorporated in 1869 and chartered as a city in 1907. The University of the State of Florida was moved from Lake City to Gainesville in 1906 and its state was simplified to University of Florida in 1909.