Urban agglomerations have gradually formed in different Chinese cities, exerting great pressure on the ecological environment. Ecosystem health is an important index for the evaluation of the sustainable development of cities, but it has rarely been used for urban agglomerations. In this study, the ecosystem health in the middle reaches of the Yangtze River Urban Agglomeration was assessed using the ecosystem vigor, organization, resilience, and services framework at the county scale. A GeoDetector was used to determine the effects of seven factors on ecosystem health. The results show that: (1) The spatial distribution of ecosystem health differs significantly. The ecosystem health in the centers of Wuhan Metropolis, Changsha-Zhuzhou-Xiangtan City Group, and Poyang Lake City Group is significantly lower than in surrounding areas. (2) Temporally, well-level research units improve gradually; research units with relatively weak levels remain relatively stable. (3) The land use degree is the main factor affecting ecosystem health, with interactions between the different factors. The effects of these factors on ecosystem health are enhanced or nonlinear; (4) The effect of the proportion of construction land on ecosystem health increases over time. The layout used in urban land use planning significantly affects ecosystem health.