First referred to as "Choctaw", the town was named after railroad financier and former Union Civil War general, Samuel Russell Thomas, after he donated $500 for the construction of Thomasville's first school.

[3] The town had expanded by the end of the 19th century with numerous stores, several hotels and boarding houses, and a depot station.

[3] The railroad discontinued its use of the town's depot by the 1950s, but that time also saw the opening of Thomasville's FPS-35 radar base, part of the Air Defense Command's Semi Automatic Ground Environment (SAGE) system, bringing in servicemen and their families.

The 1960s and 1970s saw the opening of numerous paper mills in the area, an industry that continues to be important to the economy of Thomasville today.

It is the northernmost incorporated settlement in Clarke County and is situated on an elevated area between the Tombigbee and Alabama rivers.

The climate in this area is characterized by hot, humid summers and generally mild to cool winters.

[17] The economy of Thomasville is largely based on retail trade and the service sector, with the city serving as a regional commercial hub.

[22] Coastal Alabama Community College is a state-supported, fully accredited, comprehensive two-year college serving southwest Alabama with its main campus in Atmore, The Academy at the Fairhope Airport, Bay Minette, Brewton, Fairhope, Gilbertown, Gulf Shores, Jackson, Life Tech Center, Monroeville and Thomasville.

Thomasville had one acute care hospital, Southwest Alabama Medical Center, with 50 licensed beds.

A statement released to the public after closing stated that the hospital had not made enough money to cover operating expenses.

The director of the Alabama Department of Public Health confirmed that the facility had turned in its operating license on August 16.

Thomasville Nursing Home is a 70 bed long-term care facility located on Mosley Drive.

[27] A new 68,300 square foot, 29-bed acute care hospital, Thomasville Regional Medical Center, opened on March 3, 2020.

[30] The Thomasville campus of Alabama Southern Community College is home to the Kathryn Tucker Windham Museum.