Regional ecosystem health is the basis for regular regional exploration, ecological protection, and sustainable development. This study explored ecosystem health at the southern end of the Hu Line (Sichuan and Yunnan provinces) using the pressure–state–response model and examined the spatial evolution of ecosystem health. The proportion of unhealthy and morbid cities decreased from 45.9% in 2000 to 35.1% in 2016. The imbalance of ecosystem health among cities has gradually increased since 2006, but more high-quality cities have emerged (Z of Moran’s Index < 1.96, p > 0.05). Overall, the regional ecosystem on the southeast side of the Hu Line was healthier than that on the northwest side. Differences in ecosystem health on both sides of the Hu Line showed decreasing trends over time except for the pressure score. The spatial pattern of ecosystem health moved along the Hu Line because the pressure and state scores of ecosystems were mainly determined by the natural environmental conditions. Based on the county-level assessment, the grade of imbalance within cities was divided, and those that were lagging were identified. To correct regional imbalances, a comprehensive and proactive policy framework for a smart development model was put forward in Sichuan and Yunnan.