Western China is an inland region facing the problem of water scarcity due to its distance from the sea and mountainous topography. Studying the sustainability, spatial and temporal variation and drivers of water resources in western China is an important way to identify and solve water resources problems in the region. This study constructed a water resources sustainability evaluation index system, including four subsystems and 26 indicators, to examine the spatial, regional variation and temporal evolution of water resources sustainability in 12 provinces from 2012 to 2022. The results show that: (1) interannual trends show fluctuations and differences in resources, environment and socioeconomics; (2) the scores of the water resources and socio-economic subsystems are relatively average, while the water environment subsystem shows significant differences and the water ecology subsystem scores lower; (3) the global spatial agglomeration effect shows a fluctuating and expanding trend, with a significant positive spatial autocorrelation, mainly attributed to density excesses, followed by interand intra-regional differences, leading to an uneven distribution of spatial development, concentrated in two types of spatial agglomerations. Conclusions: Studies have shown that the level of water sustainability in western China is gradually improving and that spatial and temporal differences in water indices are gradually decreasing.