Wheat is one of the founder crops of Western agriculture. This study reconstructs agronomic conditions, potential yields, and kernel weight in the beginnings of cultivation of domesticated free-threshing wheat, c. 8000 BC. The carbon and nitrogen stable isotope compositions and the dimensions of fossil grains of naked wheat (Triticum aestivum/durum) were analysed. Samples were collected in Tell Halula and Akarçay Tepe, two Neolithic archaeological sites from the Middle Euphrates (the claimed core area for wheat domestication). The samples analysed include the oldest reported remains of naked wheat. Consistently wetter conditions but lower kernel weights were found in the Neolithic compared with the present day. Besides, the estimated yields were clearly beyond what is expected from the gathering of wild stands of cereals. Patterns of phenotypic adaptation achieved by wheat after its diffusion through the Mediterranean were also assessed. On the one hand, the study looked at variation in morphophysiological traits as related to local climate in a set of 68 durum wheat landraces from the Middle Euphrates. On the other hand, an assessment was made of regional adaptation around the Mediterranean Basin in a set of 90 landraces, traditional varieties, and modern cultivars from different origins by characterizing agronomic and morphophysiological variability. Significant relationships were observed between phenotypic variation among landraces from the Middle Euphrates and both minimum temperatures and the ratio of precipitation to potential evapotranspiration of the sites of origin. In addition, consistent differences in grain yield, plant structure, and water status were found among genotypes following both north-south and east-west gradients across the Mediterranean. These differences are associated with contrasting environmental and selection pressures.