The Clayton post office was established in September 1835 with John F. Keener as postmaster.

Clayton has a rich heritage with four properties listed on the National Register of Historic Places.

[4] Governor George Wallace was born in nearby Clio and began his legal and political career in Clayton.

In March 1956, Wallace attended at the Clayton football stadium the first public meeting of the Barbour County White Citizens' Council, with an estimated 4,500 persons attending the white supremacist rally, "the largest rally in the history of the county seat.

[6] According to the U.S. Census Bureau, the town has a total area of 6.7 square miles (17.3 km2), all land.

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

[7] As of the 2020 United States census, there were 2,265 people, 569 households, and 359 families residing in the town.