The timing and drivers of vegetation dynamics and formation of no-analog plant communities during the last deglaciation in the unglaciated southeastern US are poorly understood. We present a multi-proxy record spanning the past 19,800 years from Cupola Pond in the Ozarks Mountains, consisting of replicate high-resolution pollen records, 25 AMS radiocarbon dates, and macrofossil, charcoal, and coprophilous spore analyses. Full-glacial Pinus and Picea forests gave way to no-analog vegetation after 17,400 yr BP, followed by development of Quercus-dominated Holocene forests, with late Holocene rises in Pinus and Nyssa. Vegetation transitions, replicated in different cores, are closely linked to hemispheric climate events. Rising Quercus abundances coincide with increasing Northern Hemisphere temperatures and CO₂ at 17,500 yr BP, declining Pinus and Picea at 14,500 yr BP are near the Bølling-Allerød onset, and rapid decline of Fraxinus and rise of Ostrya/Carpinus occur 12,700 yr BP during the Younger Dryas. The Cupola no-analog vegetation record is unusual for its early initiation (17,000 yr BP) and for its three vegetation zones, representing distinct rises of Fraxinus and Ostrya/Carpinus. Sporormiella was absent and sedimentary charcoal abundances were low throughout, suggesting that fire and megaherbivores were not locally important agents of disturbance and turnover. The Cupola record thus highlights the complexity of the late-glacial no-analog communities and suggests direct climatic regulation of their formation and disassembly.