A village of the Timucua people was once located south of the present city and at Manatee Springs.

The area's economy is traditionally based on agriculture, primarily farming (peanuts, watermelons, hay); ranching (cattle, hogs); dairy (milk); timber (pulpwood, lumber, turpentine) and aquaculture (fishing, oystering, crabbing).

[1] In 1860, it was renamed "Hardeetown", after Isaac P. Hardee, who was a slaver that owned a large plantation that extended for miles and the community was eventually built on the land.

[2] In July 1927, a Black man named Albert Williams was shot and then lynched by a mob.

[8] According to the United States Census Bureau, the city has a total area of 16.1 square miles (42 km2), all land.

The climate in this area is characterized by hot, humid summers and generally mild winters.

The museum is open throughout the year and the collection contains unique items like a quilt made from the ties of two former Presidents, Jimmy Carter and Gerald Ford.

[17] Chief Theatre, home to the Suwannee Valley Players, is located off of Main Street and E, Park Avenue in downtown Chiefland.

[18] The Suwannee Valley Players, the oldest community theater troupe in Levy and its adjacent counties, has performed at Chief Theatre for over 37 years.

As growth in north Florida increased during the last quarter of the twentieth century, Chiefland became a local center for shopping.

A 202,000 sq ft (18,800 m2) Walmart Supercenter was opened in 1995, and increased traffic along US 19/98 support a variety of national fast food franchises plus Best Western and Days Inn motels.

The College of Central Florida has plans for a $12 million permanent facility on 35 acres (14 ha) of donated land by the Mann family.

[22] In November 2019, two vacant parcels of land were donated by Luther Callaway's family in hopes of expanding the library facilities.

The Suwannee Valley Community Hospital is expected to cost $27 million, and Ameris Health Systems is leading the effort.