- A town, the county seat of Barbour County, Alabama; named for Georgia jurist and congressman Augustin Smith Clayton.
- A city in Contra Costa County, California, United States; named for founder Joel Henry Clayton.
- A town in Delaware; named for John M. Clayton.
- A city, the county seat of Rabun County, Georgia, United States; named for Augustin Smith Clayton.
- A city in Idaho; named for early settler Clayton Smith.
- A town in Indiana; named for Kentucky statesman Henry Clay.
- A village in Illinois; named for Henry Clay.
- A city in Iowa.
- A city in Kansas; named for the clay in the area.
- A town in Louisiana.
- A village in Michigan.
- A city, the county seat of St. Louis County, Missouri; named for landowner Ralph Clayton.
- A borough of New Jersey.
- A town, the county seat of Union County, New Mexico; named for Clayton Dorsey, son of Arkansas statesman Stephen Wallace Dorsey.
- A town and village in New York; named for lawyer and politician John M. Clayton.
- A town in North Carolina.
- A city in Ohio; named for John Clayton, a War of 1812 veteran.
- A town in Oklahoma; named for the city in Missouri.
- A town in Crawford County, Wisconsin.
- A town and village in Polk County, Wisconsin; named for Clayton Rogers, the foreman of the town's sawmill.
- A town in Winnebago County, Wisconsin.
- A suburb of Manchester, Greater Manchester, England; named for the Clayton family which owned land nearby.
- A village in South Yorkshire.
- A suburb of Newcastle-under-Lyme, Staffordshire.
- A village in Hassocks parish, Mid Sussex district, West Sussex (OS grid ref TQ2914).
- A village in West Yorkshire.
- A suburb of Melbourne, Victoria; named for proprietor John Hughes Clark.
- A habitational surname.
- A male given name transferred from the surname.
- Translingual: Claytonia