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Climate change on the Tibetan Plateau (TP) is governed by the mid-latitude westerlies and Indian summer monsoon (ISM). However, the past hydrological changes on the TP induced by interactions between the westerlies and the ISM remain unclear. A sediment core from Lake Zabuye on the southwestern TP was analyzed to reconstruct climatic and hydrological variability over the last 30 kyr. Stable isotopic compositions (δ13C and δ18O) of authigenic carbonate act as an indicator of hydrological status for closed-basin lakes on the TP. Four major climatic and hydrological stages were identified: (1) last glacial maximum (29.8–18.9 cal kyr BP), the influence of the westerlies dominated, and a cold-wet climate prevailed; (2) last deglaciation (18.9–11.8 cal kyr BP), the influence of the westerlies receded, and a general trend of decreased wetness was interrupted by two pronounced glacial meltwater events recorded at 17.2 and 15.2 cal kyr BP, respectively; (3) early and middle Holocene (11.8–3.8 cal kyr BP), the Holocene climate optimum was attained and sustained under the dominance of ISM circulation; (4) late Holocene (from 3.8 cal kyr BP to the present), the ISM collapsed during the middle to late Holocene, and a hypersaline lacustrine environment was ultimately formed, as inferred from mirabilite deposition and isotopic signals. Our lake record demonstrates an anti-phase relationships between the westerlies and the ISM on the glacial-interglacial timescale over the southwestern TP. We suggest that both North Atlantic climate and tropical ocean temperature are major drivers of climatic variations on the TP. [ABSTRACT FROM AUTHOR]