Human occupation and utilization of plant resources have affected vegetation in the lower Little Tennessee River Valley of East Tennessee for 10,000 yr. Changes in Indian cultures and land use are documented by radiocarbon chronologies, lithic artifacts, ceramics, settlement patterns, and ethnobotanical remains from 25 stratified archaeological sites within the Holocene alluvial terrace. The ethnobotanical record consists of 31,500 fragments (13.7 kg) of wood charcoal identified to species and 7.7 kg of carbonized fruits, seeds, nutshells, and cultigens from 956 features. Pollen and plant macrofossils from small ponds both in the uplands and on lower stream terraces record local vegetational changes through the last 1500 to 3000 yr. Human impact increased after cultigens, including squash and gourd, were introduced ca. 4000 yr B.P. during the Archaic cultural period. Forest clearance and cultivation disturbed vegetation on both the floodplain and lower terraces after 2800 yr B.P., during the Woodland period. Permanent Indian settlements and maize and bean agriculture extended to higher terraces 1.5 km from the floodplain by the Mississippian period (1000 to 300 yr B.P.). After 300 yr B.P., extensive land clearance and cultivation by Historic Overhill Cherokee and Euro-Americans spread into the uplands beyond the river valley.