[2] The county was established in 1837 and was named in honor of John M. Clayton,[3] United States Senator from Delaware and later Secretary of State under President Zachary Taylor.

Clayton County is part of the Driftless Area, a region that completely missed being ice-covered during the last ice age.

Streams have deeply carved valleys, while the Mississippi River has spectacular bluffs.

[11] As of the census[12] of 2000, there were 18,678 people, about 7,500 households, and 1 family residing in the county.

The racial makeup of the county was 98.93% White, 0.14% Black or African American, 0.22% Native American, 0.11% Asian, 0.01% Pacific Islander, 0.19% from other races, and 0.41% from two or more races.

26.30% of all households were made up of individuals, and 13.30% had someone living alone who was 65 years of age or older.