Gainesboro is part of the Cookeville, Tennessee Micropolitan Statistical Area.

The Gainesboro vicinity was a popular destination for long hunters as early as the 1770s, as natural salt licks drew rich game to the area.

In the 1790s, Avery's Trace passed nearby, with travellers along the road lodging at Fort Blount about 10 miles to the west.

Gainesboro was named after U.S. Army Brevet Major General Edmund P. Gaines (1777–1849).

[9] As of the 2020 United States census, there were 920 people, 347 households, and 152 families residing in the town.