The city's economic engine is the University of Florida, which is by far the largest employer in the area and brings in a large amount of state and federal money.

Gainesville, known for its strong music scene, was named "Best Place to Start a Band in the United States" by Blender magazine in March 2008. The article cited the large student population, cheap rent, and friendly venues.

Devil's Millhopper is unique in Florida in terms of its size, with over 100 feet (30 m) of rock layers are exposed. The sinkhole got its name from its appearance, which is similar to the hopper of a mill, and local legends that the bones found at the bottom were from animals who had entered the sinkhole to meet the devil. The Millhopper was owned for a time by the science department at the University of Florida and used as a research site for the students, but it was purchased by the state in 1974 and listed on the National Register of Historic Places.

The historic Hippodrome Theatre in Downtown Gainesville is now a renowned preforming arts center, but it was originally a courthouse. According to local legend, a young man went on trial for a murder he didn't commit, and his mother, who had evidence proving his innocence, rushed to town but arrived just moments after he had been hanged. According to performers at the Hippodrome, this woman, Lucinda Boyle, still haunts the former courthouse, searching for her lost son.

Gainesville is the county seat of Alachua County, Florida.