Oka Kapassa (Ococoposa), meaning "Cold Water", was the Chickasaw name given to Spring Creek and to a trading post established near the Tennessee River about 1780. About 1817, Michael Dickerson and others were greeted at what by then was called Big Spring by Chief Tuscumbia, a Chickasaw rainmaker. The settlers named the new town in his honor in 1822. Colbert County, formed in 1867 from the Northern half of Franklin County, was named for Chickasaw Chieftains George Colbert, operator of and Inn and ferry on the Natchez Trace at the Tennessee River, and his brother Levi Colbert, who ran and Inn on the Trace at Buzzard Roost Spring.
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Prehistoric "hunters and gatherers" lived in the area along the Tennessee River and its tributaries, including Spring Creek, more than 10,000 years ago. When early white settlers arrived, the area was occupied by Chickasaws to the west and Cherokees to the east. Other tribes, including the Creeks, occasionally hunted or lived briefly in the area. After the Indian Removal Act of 1830, thousands of Native Americans passed through Tuscumbia on the "Trail of Tears." The Tuscumbia, Courtland, and Decatur Railroad transported Indians to Tuscumbia Landing where they boarded steamboats for removal to new homes in the Indian Territory (now Oklahoma).