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Clay County was established on December 7, 1866, from land taken from Randolph and Talladega counties. Named after the famous statesman Henry Clay, the county seat itself was named after his estate in Lexington, Kentucky called "Ashland". The county was covered with a heavy growth of trees, and a part of the territory was occupied by the Creek Indians. The early pioneers acquired the lands by government entry and the Indian lands by public auction. The families came wholly from Fayette County, Georgia. Clay County was formed for geographic reasons. The citizens of the area had a difficult time reaching the county seat of Wedowee in Randolph County because of the Tallapoosa River to the east. Talladega was difficult to reach because of the intervening mountains. Even today, Clay County is one of only three counties in Alabama to have no U.S. highways in its boundaries. Ashland was a mining center, particularly for graphite.
During the Desert Shield/Storm conflict, Clay County had more soldiers serving per capita than any other county in the United States.