The present study documents the first confirmed fossil record of Sinomenium in Menispermaceae, Sinomenium macrocarpum sp. nov., from the recently discovered Gray Fossil Site in Tennessee, southeastern USA. The fossil species is represented by more than 120 endocarps, all of which are characterized by their horseshoe-shaped form and occurrence of highly ornamented protuberances on both dorsal and lateral crests. A combination of their relatively large size and highly developed of protuberances on the surface of endocarp warrants the new species. The new species is justified through a detailed comparison with the related and published extant and fossil species. The discovery of the genus in North America appears to support that the Gray site in southern Appalachian region represented a forest refugium during the late Neogene when the global cooling was intensified and grasslands were globally expanded.