Abstract: Global warming has led to significant glacier retreat around the Tarim River Basin and an increase in glacier meltwater. This has resulted in a rise in water resources in southern Xinjiang. Meanwhile, the development of human society has driven a substantial increase in water consumption for both production and daily living. This has disrupted the regional water supply-demand balance, making the risk of water resource stress more prominent. Given the characteristics of water resources utilization in arid areas and taking into account the changing trends in precipitation, glacial meltwater, and runoff due to climate change, along with population and economic development in southern Xinjiang, we employed the water stress index method to assess the current situation and potential future changes in water stress in the three regions of southern Xinjiang. The results indicated the following:the water availability in the three regions of southern Xinjiang increased during 2000~2020. There were regional differences in total water demand, which increased significantly in Aksu and Kashgar region, but decreased in Hotan region. The water stress in the three regions of southern Xinjiang is at a relatively high level, and the variation trend of water stress is consistent with that of total water demand. In the future (2030s and 2070s), the amount of water availability in the three regions of southern Xinjiang will continue to increase; the changing trends of water demand and water pressure are consistent with historical periods. Human water extraction activities will play a leading role in future changes in water stress. This study reveals the spatiotemporal differentiation of water resource imbalances in the regions and provides scientific reference for water resource management and rational utilization in southern Xinjiang.