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Drought occurrence and duration in central Asia are of important socioeconomic, ecological, and geophysical significance and have received increasing research attention in recent years. Understanding long-term drought trends and their driving forces require reliable records of past drought variability with broad spatial representativeness. Here, we compiled four tree-ring O-18 records from eastern central Asia (ECA) and composited them into a drought-sensitive proxy to explore regional ECA moisture variations over the past 301years (1710-2010 CE). A robust regional standardized precipitation-evapotranspiration index (SPEI) reconstruction was established based on the tree-ring cellulose O-18 fractionation mechanism and statistically significant proxy-climate relationships. We identified prominent droughts in 1710-1770, 1810-1830, and the beginning of the twenty-first century, and a regime shift to a persistently wet period from the 1880s to 2000. Our reconstruction reveals the impact of drought and pluvial patterns on the decline of Zhungar Empire, and on historical agricultural and socio-economical activities, including increased migration into ECA during the 1770-1800 pluvial. Our findings also suggest that wet conditions in the twentieth century in ECA were related to a strengthening of the westerly circulation and thus shed light on large-scale atmospheric circulation dynamics in central Asia.