St. Louis is a town in Pottawatomie County, Oklahoma, United States.
St. Louis originally began in 1906 as a community named Simpsonville when J. R. Simpson opened a cotton gin, a gristmill and then a general store. It is unclear when the name of the community was changed to St. Louis. A town plat was not filed until 1927 and a post office was established in 1928.
A town plat was filed March 9, 1927, and the community incorporated as a town some time later. The St. Louis post office was established in 1928.
Except for a brief oil boom in the 1920s, the town's economy has been based on serving local cotton farmers.
The population peaked at 493 residents in 1930 and has declined until the present.