To investigate the coordinated and sustainable development of the water resources-food-energy-ecosystem (WFEE) in the Shiyang River Basin and mitigate the negative impacts from the development of a single resource sector on other resource domains, we established a coupling and coordination evaluation index system for the WFEE system of the northwest inland Shiyang River Basin as a case study. The CRITIC method was employed for the weighting of subsystem indicators, and the coupling coordination degree model was adopted to analyze the spatiotemporal evolution characteristics and the coordination degree of Shiyang River Basin’s WFEE from 2020 to 2030. Results demonstrate that the comprehensive development index of the Shiyang River Basin’s WFEE system from 2000 to 2020 was at a moderate level, with the energy subsystem showing a negative growth trend. The WFEE system of Shiyang River Basin has undergone six stages, from mildly disordered to well coordinated, displaying an upward trend. The prediction results suggest that the basin will remain a well-coordinated growth trend during the forecast period from 2020 to 2030. These findings provide a scientific basis for the sustainable management and efficient development and utilization of the Shiyang River Basin.