Ecosystem health (EH) is important for ensuring sustainable development, and the main goal of environmental protection and governance, especially for ecological fragile areas. Scientific assessment of EH can improve decision-making ability and inform sustainable development. In this paper, the effects of natural and social environment were integrated to reflect the characteristics of EH based on a comprehensive assessment system including ecosystem vigor (EV), ecosystem organization (EO), ecosystem resilience (ER), and the ratio of supply to demand of ecosystem services (ESDR) from the perspectives of ecological integrity and human demand for ecosystem services (ES). The Entire-Array-Polygon (EAP) method was applied to calculate an ecosystem health index (EHI) and analyze spatio-temporal change from 2000 to 2020 in Hexi Corridor (HC), Northwest China. The results showed that: (1) The spatial distribution of EV, EO, ER, and ESDR was generally consistent, with a low spatial distribution in the northwest and high in the southeast, the values showed an overall increasing trend from 2000 to 2020. (2) The spatial distribution of EHI was high in the northwest and central regions, and low in the southwest, reflected a moderate health level. The proportion of area with well and relatively well health was increasing, which indicated that EH showed an improving trend. (3) The significantly decrease areas of EHI were mainly located in urban areas, and the increases areas were mainly located outside of urban areas. The distribution of the EH condition has obvious orientation characteristics. The results of the study provide theoretical and practical implications for regional ecological conservation and management.