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The collapse and resilience of political systems in the ancient Near East and their relationship with agricultural development have been of wide interest in archaeology and anthropology. Despite attempts to link the archaeological evidence to local paleoclimate data, the precise role of environmental conditions in ancient agricultural production remains poorly understood. Recently, stable isotope analysis has been used for reconstructing site-specific ancient growing conditions for crop species in semiarid and arid landscapes. To open the discussion of the role of regional diversity in past agricultural production as a factor in societal development, we present 1.037 new stable carbon isotope measurements from 33 archaeological sites and modern fields in the geographic area of the Fertile Crescent, spanning the Aceramic Neolithic [10,000 calibrated years (cal) B.C.] to the later Iron Age (500 cal B.C.), alongside modern data from 13 locations. Our data show that drought stress was an issue in many agricultural settlements in the ancient Near East, particularly in correlation with the major Holocene climatic fluctuations, but its regional impact was diverse and influenced by geographic factors. Although cereals growing in the coastal areas of the northern Levant were relatively unaffected by Holocene climatic fluctuations, farmers of regions further inland had to apply irrigation to cope with increased water stress. However, inland agricultural strategies showed a high degree of variability. Our findings suggest that regional differences in climatic effects led to diversified strategies in ancient subsistence and economy even within spatially limited cultural units. [ABSTRACT FROM AUTHOR]