Ecosystem services in arid inland regions are significantly affected by climate change and land use/land cover change associated with agricultural activity. However, the dynamics and relationships of ecosystem services affected by natural and anthropogenic drivers in inland regions are still less understood. In this study, the spatiotemporal patterns of ecosystem services in the Hexi Region were quantified based on multiple high-resolution datasets, the InVEST model and the Revised Wind Erosion Equation (RWEQ) model. In addition, the trade-offs and synergistic relationships among multiple ecosystem services were also explored by Pearson correlation analysis and bivariate spatial autocorrelation, and redundancy analysis (RDA) was also employed to determine the environmental drivers of these services and interactions. The results showed that most ecosystem services had a similar spatial distribution pattern with an increasing trend from northwest to southeast. Over the past 40 years, ecosystem services in the Hexi Region have improved significantly, with the water retention and soil retention increasing by 87.17 × 10⁸ m³ and 287.84 × 10⁸ t, respectively, and the sand fixation decreasing by 369.17 × 10⁴ t. Among these ecosystem services, strong synergistic relationships were detected, while the trade-offs were found to be weak, and showed significant spatial heterogeneity in the Hexi Region. The spatial synergies and trade-offs in the Qilian Mountains were 1.02 and 1.37 times higher than those in the Hexi Corridor, respectively. Human activities were found to exacerbate the trade-offs between ecosystem services by increasing water consumption in the Hexi Corridor, with the exception of carbon storage. In particular, there were significant tradeoffs between food production and water retention, and between soil retention and habitat quality in the oases of the Hexi Corridor, which is affected by rapid population growth and cropland expansion. Additionally, precipitation, temperature and vegetation cover in the Qilian Mountains have increased significantly over the past four decades, and these increases significantly contributed to the enhancements in water retention, carbon storage, habitat quality, soil retention and food production. Nevertheless, the amount of sand fixation significantly decreased, and this was probably associated with the reduction in wind speed over the past four decades. Our results highlighted the importance of climate wetting and water resource management in the enhancement of ecosystem services and the mitigation of food production trade-offs for arid inland regions.