In recent years, due to the increasing intensity of marine economic activities, such as port construction, land reclamation, and mariculture, bay ecosystems have been increasingly influenced by ecological and environmental threats. However, our current understanding of the ecosystem health level and its associated mechanisms are still insufficient in Haizhou Bay, China. Therefore, it is necessary to construct a comprehensive health framework to integrate and explain the dynamic changes in ecosystem health over a wider range. In this study, we established a comprehensive ecological health indicator system to calculate the ecosystem health index (EHI) for Haizhou Bay during 2012–2018 using the pressure–state–response (PSR) framework. Correlation analysis and barrier models were combined to explore the factors that affected sustainable development of the Haizhou Bay ecosystem. The EHI for Haizhou Bay was in a moderately healthy state during 2012–2018, with an overall increase of 25%, which indicated that the health quality of the ecosystem improved slightly. The pressure (+0.1073) and state (+0.1185) increased from moderately healthy to a relatively healthy state, and the response (+0.0866) was in a moderately healthy state. The three factors comprising industrial wastewater discharge, organic pollution index, and nutrition level index had the highest obstacle degrees during the study period, and the EHI had high correlations with land-based pollution (+0.79) and seawater quality (+0.75), which were the main factors that influenced the ecological health of Haizhou Bay. Our new evaluation framework developed for studying bay ecosystem health can be extended and applied to other bays with similar conditions. Our findings can also be used to provide recommendations for the conservation and management of the Haizhou Bay ecosystem, thereby contributing to its sustainable development.