Global warming has led to significant glacier retreat around the Tarim River Basin. 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. 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, along with population and economic development, 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 synergistic effects of precipitation and glacial meltwater have significantly increased river runoff, resulting in increased available water. The total water demand in the Aksu and Kashgar regions has shown a substantial increase, while the Hotan region has experienced a decrease. The Aksu and Kashgar regions have exhibited an upword trend in water stress, while the Hotan region has seen some relief. Nevertheless, all the three regions still face high water stress levels. In comparison to the historical period (2000-2020), the available water and total water demand are projected to increase during the next four periods (2030s, 2050s, 2070s and 2090s) under the SSP2-4.5 and SSP5-8.5 scenarios of the CMIP6 model. Notably, the Aksu region is expected to face increasing water stress, indicating a significant risk of water scarcity and insecurity in the future.