We measured 10Be in fluvial sediment samples (n = 27) from eight Great Smoky Mountain drainages (1–330 km2). Results suggest spatially homogeneous sediment generation (on the 104–105 yr time scale and >100 km2 spatial scale) at 73 ± 11 t km−2 yr−1, equivalent to 27 ± 4 m/m.y. of bedrock erosion. This rate is consistent with rates derived from fission-track, long-term sediment budget, and sediment yield data, all of which indicate that the Great Smoky Mountains and the southern Appalachians eroded during the Mesozoic and Cenozoic at ∼30 m/m.y. In contrast, unroofing rates during the Paleozoic orogenic events that formed the Appalachian Mountains were higher (≥102 m/m.y.). Erosion rates decreased after termination of tectonically driven uplift, enabling the survival of this ancient mountain belt with its deep crustal root as an isostatically maintained feature in the contemporary landscape.