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.

On January 9, 1836, the Alabama legislature created Cherokee County with its present boundaries.

[3] 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.

Cherokee County was in the news again on Palm Sunday, March 27, 1994, when it was hit by a F4 tornado.

Goshen United Methodist Church was destroyed only twelve minutes after the National Weather Service at Birmingham had issued a warning for northern Calhoun, southeastern Etowah, and southern Cherokee counties.

There are approximately 3,800 students in public K-12 schools in Cherokee County.

Gadsden State Community College operates a campus located in Centre.

School districts include:[16] Historically Democratic, Cherokee County became competitive by the end of the 20th century and is now reliably Republican at the presidential level.

The last Democrat to win the county in a presidential election is Bill Clinton, who won it by a comfortable margin in 1996.