The present town of Fort Gaines was founded in 1816 as protection against the indigenous Creeks and prospered due to riverboat trade.

[5] Though it was named for General Edmund Pendleton Gaines, he did not arrive there with the 4th Infantry of the United States Army until 1816.

In 1854, Fort Gaines was designated seat of the newly formed Clay County.

"The writer esteems that the society and location of Fort Gaines for literary purposes, so far as the education of youths is concerned, equal to that of Sparta [Georgia].

GA-266 begins just north of the city and leads northeast 22 mi (35 km) to Cuthbert.

[10] As of the 2020 United States census, there were 995 people, 336 households, and 212 families residing in the city.

[26] High school aged students attend 10-12th grade in adjoining Randolph County, Georgia.