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The area included in today's Cherokee County, for centuries, had belonged to the Muscogee (Creek) Nation of Native Americans. Cherokees began moving into the area a generation before the forced Indian Removal. To this day, there are few Native Americans in Cherokee County.
On January 9, 1836, the Alabama legislature created Cherokee County with its present boundaries. Two years later, the United States government removed, by force, all Cherokees who had refused to leave on what would become known as the Trail of Tears.