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Gainesville was established in 1853 and named for General Edmund P. Gaines, a U.S. Army commander from the Seminole Wars era, and it has served as the Alachua County seat since 1854 before incorporating as a city in 1869.

Gainesville had a population of 141,085 in the 2020 Census, and Census Bureau estimates put it at about 148,671 by 2025, making it the largest city in Alachua County.

Gainesville has about 59,816 households averaging just 2.14 people each, and only about 38% of its homes are owner-occupied - one of the lowest rates of any Florida city, because so many residents are university students - with a median owner-occupied home value of $247,500.

The University of Florida traces its roots to the East Florida Seminary of 1853, was created in its modern form under the Buckman Act of 1905, and opened its Gainesville campus in September 1906 with just 102 students.

Gatorade was invented at the University of Florida in 1965 by researchers working to help the Gators football team fight dehydration, and the drink's royalties have since earned the university hundreds of millions of dollars.

Santa Fe College, founded in Gainesville in 1966, won the 2015 Aspen Prize as the nation's number one community college.

Santa Fe College runs the Santa Fe College Teaching Zoo, the only nationally accredited zoo located on a college campus in the United States.

Kanapaha Botanical Gardens, opened in 1986 across 62 acres, holds Florida's largest public display of bamboo and the largest herb garden in the Southeast.

Paynes Prairie Preserve State Park, a vast savanna famous for herds of wild horses and bison, sits at Gainesville's southern edge.

Devil's Millhopper Geological State Park protects a giant limestone sinkhole about 120 feet deep and 500 feet across that visitors descend into on 232 wooden steps; designated a National Natural Landmark, it has yielded fossils of shark teeth, marine shells and extinct land animals.