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Climate change and its impact on plateau lakes are of wide concern in China owing to their diverse yet fragile ecosystems. The three largest and most concerning plateau lakes (Dianchi, Erhai, and Fuxian lakes) in southwestern China were selected as case studies to demonstrate their different hydrological responses attributing to the local climatic and watershed characteristics. We processed 27 climate change scenarios according to the local climate characteristics and simulated the daily runoff of each lake basin under the historical and the 27 climate change scenarios. Then we analyzed the change of mean annual and seasonal runoff, and hydrological extremes of each lake basin. The results indicate a great risk of socio-economic and ecological for these plateau lakes as climate change will significantly alter the horological regimes of each lake basin. The mean annual runoff of the three lake basins will change from–65.24 to 54.17 %, when the air temperature increases by 1–2 °C and precipitation changes from –20 to + 20 %. Climatic and topographic heterogeneities caused each lake basin responded differently to climate change. Among them, the LFB was more sensitive to climate change than the LDB and LEB. Changes in the annual and seasonal runoff for the LFB were approximately 1.5-fold higher than that of the LDB and LEB. The hydrological extremes in the LFB also had the most significant changes. To cope with future climate change, each lake requires reasonable and effective mitigation measures.