The Oconaluftee River drains the south-central Oconaluftee valley of the Great Smoky Mountains in Western North Carolina before emptying into the Tuckasegee River. The river flows through the Qualla Boundary, a federal land trust that serves as a reserve for the Eastern Band of the Cherokee, the only federally recognized tribe in North Carolina. They bought the land back from the federal government in the 1870s, after having been pushed off and forced to cede it earlier in the 19th century. Several historic Cherokee towns are known to have been located along this river.

The Oconaluftee is the valley of the Oconaluftee River in the Great Smoky Mountains of North Carolina. Formerly the site of a Cherokee village and an Appalachian community, the valley is now North Carolina's main entrance to Great Smoky Mountains National Park.