In developing countries, urban agglomerations have become one of the most important carriers of urbanization. In China, one of the largest national urban agglomerations is the UAMRYR (urban agglomeration in the middle reaches of the Yangtze River), which has the fastest urban development in Central China and is home to critical ecological spaces. On this basis, this study analyzed the urban expansion and loss of ecological lands in UAMRYR by establishing a spatial database, grid system, rose maps, and scenario simulation. The highlights of results are as follows: the urban expansion of UAMRYR includes four stages of development: steady growth, accelerated development, peak, and deceleration. Polarized development has occurred in the region, with the Wuhan, Changsha-Zhuzhou-Xiangtan, and Nanchang metropolitan areas having high levels of urban expansion while the other cities have varying levels of urban growth. The loss of ecological land was found to have a highly similar curve and spatial distribution with the urban growth. In terms of ecological land types, the loss of agricultural land accounted for more than half of ecological lands lost overall. Losses in forests, grasslands, wetlands, and water areas varied for different areas, depending on particular conditions and specific environmental characteristics of the city. The three metropolitan areas experienced the highest increases in urban built-up areas; they also had the highest loss of ecological land, which can have critical consequences given their proximity to the Yangtze River, Poyang Lake, Dongting Lake, and other important environmental sensitive areas. The simulation results show that the UAMRYR is projected to maintain a rapid expansion rate from 2020 to 2030. If the urban expansion, particularly in the metropolitan areas, is not managed well and controlled, serious ecological damage could be inflicted on the Yangtze River Basin.