The appearance of agriculture in the Fertile Crescent propelled the development of Western civilization. Here we investigate the evolution of agronomic conditions in this region by reconstructing cereal kernel weight and using stable carbon and nitrogen isotope signatures of kernels and charcoal from a set of 11 Upper Mesopotamia archaeological sites, with chronologies spanning from the onset of agriculture to the turn of the era. We show that water availability for crops, inferred from carbon isotope discrimination (Δ(13)C), was two- to fourfold higher in the past than at present, with a maximum between 10,000 and 8,000 cal BP. Nitrogen isotope composition (δ(15)N) decreased over time, which suggests cultivation occurring under gradually less-fertile soil conditions. Domesticated cereals showed a progressive increase in kernel weight over several millennia following domestication. Our results provide a first comprehensive view of agricultural evolution in the Near East inferred directly from archaeobotanical remains.