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Understanding historical hydroclimate change during the last millennium is of fundamental importance for forecasting and evaluating the regional hydrologic cycle and water security under global warming. Here we compared observations of tree-ring stable isotope ratios (delta C-13 and delta O-18), tree-ring widths, lake sediments estimates of regional hydroclimate, and glacier advance and retreat for northeastern Qinghai-Tibetan Plateau, China. The hydroclimate dynamics in our composite isotope record is similar to that derived from the juniper tree-ring widths throughout the last millennium until the latter half of the twentieth century, after which they diverged with the tree-ring widths indicating an unprecedented wet period while the isotopic results, sediment proxies, and glaciers demonstrated a drying pattern. Rising atmospheric CO2 promoted increases in canopy-scale intrinsic water-use efficiency and growth, causing tree-ring widths to overestimate the regional hydroclimate signal in the growth record. Thus, our study suggests that CO2 fertilization over the last century may confound hydroclimate reconstructions inferred from juniper tree-ring width at northeastern Qinghai-Tibetan Plateau, which may cause overestimates of water resources. Correction for CO2-induced changes in tree-ring widths may be necessary to accurately utilize tree rings for paleoclimate reconstructions.