Thomaston was incorporated on June 11, 1825, and designated as the seat of Upson County. Located in West Central Georgia, on U.S Highway 19, Thomaston is located only 68 miles south of Atlanta, 47 miles west of Macon, 60 miles north-east of Columbus, and 12 miles east of the Flint River. The town was named after General Jett Thomas, an Indian fighter in the war of 1812. The town was laid out with parallel streets running north and south, east and west, with the courthouse square at the center of town. The Judges of the Inferior Court had the authority to sell lots to individuals on a one-third cash basis with two years to complete the payment. This money was used to build the first courthouse in 1828. The second courthouse was build in 1852, and the current courthouse in 1908.

The oldest building in Thomaston stands on the corner opposite the courthouse at the East Gordon and Center Street intersection. This two story brick building was built by Dr. John L. Cheny. The famous Cheny Expectorant, which became a household remedy in the south, was manufactured in this building. This building also had the first telephone exchange in the city. The building is now known as the Fincher Building.

On April 18, 1865, nine days after General Robert E. Lee surrendered at Appomattox, Virginia, Union raiders spent three days devastating Thomaston. The Union Cavalry was heading from Columbus to Macon were led by Major General James Harrison Wilson. They destroyed three cotton mills and set fire to a steam locomotive.

After the Civil War, Thomaston grew into a large livestock trading center. It was known as the Mule Capitol of Georgia and was second only to St. Louis in the number of mules traded. Sale barns occupied much of the present-day business section of Thomaston because of this trade. The pioneer families that helped develop this livestock trade were Black, Britt, Colquitt, Hightower, Parks, Crawford, Pasley, and Thompson.

In 1899 Thomaston Cotton Mills was granted a charter. At this time most of the economy of Thomaston was based on textiles. This mill shipped textiles worldwide and was a major source of economic stability and growth. Martha Mills was another big part of the economy with their B. F. Goodrich tire cord mill. East Thomaston (Thomaston Mills) and Silvertown (Martha Mills) were typical of southern mill towns at the time. The mill-town era ended in 2001 when Thomaston Mills, Thomaston's main employer, declared bankruptcy.

Currently the population of Thomaston is stable at around 9,500, despite the closing of the mills. Many of the former employees enrolled at Flint River Technical College to learn skills to help them find other employment. There are also other industries that have opened such as Quad Graphics, Duni, and Yamaha.