As the main channel of matter exchange between riverine and marine environments, estuarine ecosystems have been subjected to growing environmental interference and disturbance. Anthropogenic activities and the interactions between land and sea considerably affect estuarine ecosystems and health, and they have resulted in challenges for ecosystem management. Ecosystem health assessment, a new method of ecosystem assessment, determines the current ecosystem structure and function, and provides substantial information necessary for effective ecosystem management. Therefore, for the management of the Yellow River Estuary, a pressure-state-response (PSR) method was used to assess the health status of the ecosystem. The estuary and the adjacent marine and terrestrial ecosystems were considered an entity under the broad definition of estuarine ecosystems. An ecosystem health assessment indicator system was developed, taking external pressure, ecosystem state, and response parameters into consideration to calculate indicators of regional ecosystem health. The health status of the Yellow River estuarine ecosystem was then assessed using a comprehensive evaluation index (CEI), including historical data from 1991. The results showed that the overall index of the Yellow River Estuary was 0.7427 in October 2013. In detail, the response index was 0.9055, which indicates that the Yellow River estuarine ecosystem was "very healthy," suggesting the policy and behavior of local government, relevant departments, and individuals reduced the pressure on the regional environment to a certain extent. The pressure index was 0.8288, which indicates that the ecosystem was at a "good status," but has been under growing pressure and its health has deteriorated. The state index was 0.6458, suggesting that the ecosystem is "unhealthy" and is under considerable pressure, requiring improvement. Overall, the current status of the Yellow River estuarine ecosystem was reasonably "healthy" as compared to that in 1991, but it has deteriorated. The state index showed the most serious decline among pressure, state, and response indexes. The main reasons for the health degradation of the Yellow River estuarine ecosystem were investigated by analyzing the index variation and its weight. The factors resulting in the deterioration included overfishing, unreasonable wetland development, over-farming in shallow seawater, and pollution. Therefore, actions should be taken to prevent further deterioration through ecological restoration and appropriate management of the Yellow River estuarine ecosystem. Any future development should be based on scientific planning for the sustainability of the ecosystem.