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Glacial lakes are important freshwater resources in southern Tibet. However, glacial lake outburst floods have significantly jeopardized the safety of local residents. To better understand the changes in glacial lakes in response to climate change, it is necessary to conduct a long-term evaluation on the areal dynamics of glacial lakes, assisted with local observations. Here, we propose an innovative method of classification and stacking extraction to accurately delineate glacial lakes in southwestern Tibet from 1990 to 2020. Based on Landsat images and meteorological data, we used geographic detectors to detect correlation factors. Multiple regression models were used to analyze the driving factors of the changes in glacier lake area. We combined bathymetric data of the glacial lakes with the changes in climatic variables and utilized HEC-RAS to determine critical circumstances for glacial lake outbursts. The results show that the area of glacial lakes in Nyalam County increased from 27.95 km2 in 1990 to 52.85 km2 in 2020, and eight more glacial lakes were observed in the study area. The glacial lake area expanded by 89.09%, where we found significant growth from 2015 to 2020. The correlation analysis between the glacial lake area and climate change throughout the period shows that temperature and precipitation dominate the expansion of these lakes from 1990 to 2020. We also discover that the progressive increase in water volume of glacial lakes can be attributed to the constant rise in temperature and freeze–thaw of surrounding glaciers. Finally, the critical conditions for the glacial lake’s outburst were predicted by using HEC-RAS combined with the changes in the water volume and climatic factors. It is concluded that GangxiCo endures a maximum water flow of 4.3 × 108 m3, and the glacial lake is in a stable changing stage. This conclusion is consistent with the field investigation and can inform the prediction of glacial lake outbursts in southwestern Tibet in the future.