The Native American tribe that originally inhabited the southern Appalachian Mountains is the Cherokee.

The Cherokee people have a deep historical and cultural connection to the southern Appalachians, particularly in areas that are now North Carolina, Tennessee, Georgia, and South Carolina. They developed a rich culture, including a unique language, social structure, and traditions that are still celebrated today. The Cherokee played a significant role in the history of the region, especially during European colonization and the subsequent events that led to the Trail of Tears in the 1830s, which forcibly removed many Cherokee from their ancestral lands.