Urban ecosystem health evaluation can assist in sustainable ecological management at a regional level. This study examined urban agglomeration ecosystem health in the middle reaches of the Yangtze River with entropy weight and extension theories. The model overcomes information omissions and subjectivity problems in the evaluation process of urban ecosystem health. Results showed that human capital and education, economic development level as well as urban infrastructure have a significant effect on the health states of urban agglomerations. The health status of the urban agglomeration's ecosystem was not optimistic in 2013. The majority of the cities were unhealthy or verging on unhealthy, accounting for 64.52% of the total number of cities in the urban agglomeration. The regional differences of the 31 cities' ecosystem health are significant. The cause originated from an imbalance in economic development and the policy guidance of city development. It is necessary to speed up the integration process to promote coordinated regional development. The present study will aid us in understanding and advancing the health situation of the urban ecosystem in the middle reaches of the Yangtze River and will provide an efficient urban ecosystem health evaluation method that can be used in other areas.