Water resources in arid and semi-arid inland regions are highly vulnerable, facing threats from global climate change and human activities. Ensuring water resource sustainability requires scientifically evaluating the vulnerability of water resources and its driving factors. Taking the Shule River Basin, an inland river in northwest China, as an example, this study established an assessment system considering 16 influencing factors based on three aspects, including natural vulnerability, anthropogenic vulnerability, and carrying capacity vulnerability. The mature-element fuzzy model based on comprehensive weight and the Delphi method were used to evaluate the water resource vulnerability of the basin from 2005 to 2021. The results were as follows: (1) The water resource vulnerability in the Shule River Basin was between severe and moderate from 2005 to 2021, with a trend towards severe vulnerability. (2) The barrier analysis at the index level shows that factors of natural vulnerability had a low impact on water resource vulnerability in the basin from 2005 to 2019 but exerted a greater impact in 2020–2021, an impact that was far higher than that caused by factors of man-made vulnerability and water resource vulnerability. The impact of factors of anthropogenic vulnerability on water resource vulnerability was relatively low in the entire study period, except in 2016, 2017, 2020, and 2021. In 2005–2010, the factors of bearing capacity vulnerability had a great impact on water resource vulnerability, but in 2011–2021, the impact was alleviated and was gradually reduced. (3) Among the 16 factors affecting water resource vulnerability, the obstacle degree was higher than 6.5% for the following factors: the ratio of irrigation water use on farmland, the annual precipitation, total water resources, the annual quantity of wastewater effluent, the urbanization rate, the surface water control rate, and the degree of groundwater resource amount, exploration, and utilization obstacle values.

Water ecological security is intricately connected to regional economic development and human survival, exerting a profound influence on regional sustainability. Water ecological security in the study area is a matter of urgency. In this study, the socio-economic, ecological, and water resource data of five cities in the west of the river from 2006 to 2021 are used to construct a dynamic model of the regional water ecological security system and simulate the trend of the regional water ecological security from 2022 to 2035, and the results indicate the following: (1) From 2006 to 2021, Hexi Corridor’s economy exhibited a significant upward trend, while its total population experienced a marked decline. Indicators for the ecological environment system showed notable improvement, whereas those for the water resource system demonstrated a significant downward trend. (2) Spatially, the mean values of system indices in the southeast and northwest regions were higher than those in the central region. (3) Between 2022 and 2035, projections reveal that the total GDP, industrial added value, average sewage discharge, urban green space, and water consumption for ecological purposes will all trend upward. Concurrently, the total population, total water supply, and total water demand are expected to exhibit a continuous decline. (4) The comparative comprehensive scores of the scenario models are as follows: EPS (2.18) > RSS (1.57) > CDS (1.15) > EDS (1.08). This analysis provides valuable insights into the dynamics of water ecological security in the Hexi Corridor and offers critical guidance for sustainable regional development planning.