The land now occupied by Charleston and Bradley County was home to the Cherokee long before European settlers arrived.

[10] In the 1820s and 1830s, many white settlers began to move into the area anticipating a future forced removal of the Cherokee by the Federal Government.

During the summer of 1838, thousands of Cherokees from various locations were held in internment camps at the fort under the supervision of federal troops before starting their journey westward, which became known as the Trail of Tears.

Several other internment camps were located in the valleys between Charleston and present-day Cleveland, Tennessee over a distance of 12 miles (19 km), including one at nearby Rattlesnake Springs.

[12] During the Civil War the Henegar House, the oldest remaining brick structure in Bradley County, was used as headquarters by both Union and Confederate generals including William T. Sherman, Oliver O. Howard, Marcus J. Wright, and Samuel Bolivar Buckner.

[13] The Charleston Cumberland Presbyterian Church building was used as a hospital by Confederate Forces in 1863.

[17] Charleston is situated along the south bank of the Hiwassee River, which flows down out of the Blue Ridge Mountains several miles to the east and empties into the Chickamauga Lake impoundment of the Tennessee River several miles to the west.

Calhoun, Charleston's sister city, is situated on the north bank of the Hiwassee, on the McMinn County side.

Interstate 75, which roughly parallels U.S. 11 in the area, runs about 2 miles (3.2 km) west of Charleston, and is connected to the city by State Route 308.

The climate in this area is characterized by hot, humid summers and generally mild to cool winters.

The city is across the Hiwassee River from a large paper mill operation of Resolute Forest Products in Calhoun, which is a major local employer.

Charleston is the postal address of the international headquarters of the Christian denomination The Church of God, commonly called "The Church of God (Charleston, Tennessee)" to distinguish it from other similarly named denominations.

An Amazon Fulfillment Center, located off the interstate in Charleston, employs several hundred people.

Germany-based chemical company Wacker Chemie broke ground in 2011 on a new solar-grade polysilicon production facility (550-acre Greenfield site).

[23] The Hiwassee River Heritage Center in Charleston, opened in 2013, showcases the history of the Cherokee Nation and Removal in the area.