Hydrology is a critical environmental condition for the evolution of wetland ecosystems. The effects of hydrological changes on wetland cover are of great importance for preserving its ecological functions. In this study, the hydrological influences on wetland cover distribution and transition in a large complex lake–floodplain system, Poyang Lake (China), were investigated. Utilizing time-series satellite remote sensing observations, wetland cover types in Poyang Lake during 2000–2009, including water, mudflat, and the major vegetation communities, were extracted and related to the wetland hydrological characteristics calculated by the hydrodynamic simulations. The statistical results of annual inundation conditions for different wetland cover types indicated that vegetation communities were preferential to hydrological environments with shorter annual inundation than water and mudflats, and different vegetation communities were distributed in areas with considerable variations in annual inundation, which suggested a substantial hydrological influence on the distribution of wetland cover in Poyang Lake. Furthermore, this study investigated the impact of hydrological changes on the wetland cover transitions between typical dry and wet years. The results showed that hydrological fluctuations had various degrees of influences on different types of wetland cover transformation. The spatial analysis indicated that hydrological changes were probably the dominant factor for the wetland cover evolution in the floodplain areas of the northern and central parts of Poyang Lake, but not the unique determined factor for wetland cover transitions in the shallow floodplains near the sink of the inflows in the eastern and southwestern parts of Poyang Lake. This study provides a practical reference for the effects of hydrological regulation in the protection and restoration of Poyang Lake wetland.