The land on which the town of Gainesville now stands was originally owned by John Coleman, husband to a Choctaw Indian of the area. He sold the land to Colonel Moses Lewis, who had the town divided into lots. The town was named for Colonel George Strother Gaines, who was an American Agent to the Choctaw Indians and had helped negotiate the Treaty of Dancing Rabbit Creek.
The town grew very rapidly and by 1840 had become the third largest town in the state of Alabama, with a population of over 4,000. The town had one of the first banks in the state which actually issued currency. Gainesville was also a major port, shipping 6,000 bales of cotton to Mobile each year by steamboats on the Tombigbee River.
The Confederate Cemetery in town is the final resting place of 250 Civil War soldiers who were injured in the Battle of Shiloh and brought to the hospital in the Female Academy in Gainesville.
Many historic homes and churches remain in Gainesville today. The town hosts "Heritage Days" every March in cooperation with the Sumter County Historical Society.
The small town of Gainesville is located on Hwy 39 in Sumter County, near the Sumter/Greene County line.