The origins of the main cultivar groups of Vitis vinifera, their relationships with wild grapevine populations, and the use of other Vitaceae are relevant issues for the improvement and conservation of Vitis diversity. Morphometric studies, domestication indices, multivariate analyses, and Bayesian hypothesis testing have been used. Eight different seed types have been identified in the 24 samples analyzed from materials from the Upper Euphrates sites of Tell Khâmis and Tell Qara Quzaq (Early Bronze Age to Hellenistic), ranging from highly domesticated to purely wild. We have been able to establish the predominance among the domesticated of Proles orientalis Negrul (three samples, Domestication Index = 1), the existence of and extinct Proles euphratica (six samples, Domestication Index = 0.67–0.83) and numerous intermediates and hybrids (eight samples). We have determined the continued presence throughout the period studied of wild grapevines related to Vitis sylvestris C.C.Gmelin and V. caucasica Vavilov (5 samples, with Domestication Indices = 0.17–0.5). The existence of Ampelopsis seeds was established for three samples. We determined that the oldest Vitaceae seed linked to human presence, in the Acheulense (780 myr), also belongs to Ampelopsis. Finally, “stenosperms” appear associated with Ampelopsis seeds (three samples), suggesting anomalies in seed formation due to intergeneric cross-pollination. Moreover, if isolated, they suggest the presence of “stenospermocarpic” Vitis vinifera raisins of the Sultanina type. Finally, we must reflect on the role that Ampelopsis species may have played and their possible cultivation and domestication almost 4000 years ago.