While the city's official spelling is one word ("LaFollette")—after its founders, Harvey Marion LaFollette and his younger brother Grant LaFollette—several federal agencies spell the city's name with two words ("La Follette").

Harvey and Grant LaFollette purchased 37,000 acres (150 km2) at Big Creek Gap, where the present community lies, around 1890.

On May 10, 1904, a major fire that started in the Cumberland Inn burned down most of the downtown area, with a reported 31 businesses destroyed.

[10] The city is situated in Powell Valley, where the Appalachian Ridge-and-Valley province gives way to the Cumberland Plateau region.

A leg of the Cumberland Trail is accessible off Tennessee Avenue at the north end of LaFollette.

According to the United States Census Bureau, the city has a total area of 4.9 sq mi (12.7 km2), all land.

As of the 2020 United States census, there were 7,430 people, 2,797 households, and 1,821 families residing in the city.