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Regional ecological health, the core of comprehensive ecosystem assessments, is an important foundation for regional exploration, environmental conservation, and sustainable development. The mountainous areas in southwest China are backward in economy, but industrialization and urbanization have been rapid in recent years. This study assessed the ecosystem health of the Sichuan and Yunnan provinces in China using a pressure-state-response (PSR) model. Spatiotemporal patterns of regional ecosystem health were analyzed from 2000 to 2016, including overall characteristics as well as local characteristics. Ecosystem health in most regions was improved over time (Y = 0.0058X − 11.0132, R2 = 0.95, P < 0.001), and areas with poorer ecosystem health decreased from half to one-third of the total area. Analysis of the primacy ratio and the variation coefficient confirmed that the gap in health scores between regions has gradually expanded since 2007, but there are more high quality regions overall (Z of Moran's index < 1.96, P > 0.05). Overall, the regional ecosystems to the east of the Hu line—an imaginary line dividing east and west China into roughly equivalent parts—were healthier than those to the west. The pressure and state scores of ecosystems were determined by physiographic condition, and the response scores by government policies and social concern. The spatiotemporal patterns of ecosystem health were dominated to a greater extent by natural than anthropogenic factors, which explains why the shift in the patterns aligned with the direction of the Hu line. Dividing regions into key management areas based on natural geographical conditions and socioeconomic development could contribute to the formulation of a reasonable ecological and environmental protection policy, guaranteeing ecosystem services in the long run. [ABSTRACT FROM AUTHOR]