Clayton is a city in Clayton County, Iowa, United States. The population was 45 at the 2020 census, down from 55 in 2000. Clayton is locateā¦Clayton is a city in Clayton County, Iowa, United States. The population was 45 at the 2020 census, down from 55 in 2000. Clayton is located directly on the Mississippi River and is only accessible via a very steep road.