Alachua County is in north central Florida. The county seat is Gainesville, home of the University of Florida and Santa Fe College. Alachua County has a total land area of 874.25 square miles with another 94.88 square miles of water surface.

Historically, this area was in the heart of the property occupied by the Timucua, a pre-Colombian tribe who were probably the only indigenous witnesses to the landing (near what is now St. Augustine) of Juan Ponce de Leon in 1513. Between 1513 and 1700, the Timucua population was reduced from around 50,000 (by one estimate, 200,000 by another estimate) to about 1,000 people, mainly through the devices of warfare and disease. By 1752, only 26 Timucua remained alive and shortly after the United States came into possession of Florida in 1821, the tribe was completely extinct. The name "Alachua" is from a Timucuan word meaning "sinkhole."

About 1740, the Oconees (root tribe of what became the Seminoles) arrived and took up residence. Alachua County was formed in 1824. Planned construction of a railroad between Cedar Key and Fernandina caused most local businesses to locate in Gainesville (on the route of the proposed railroad), and Gainesville became the county seat in 1854. The Florida Railroad finally arrived in 1859.