Abstract: Starting with the stage identification and transformation process division of regional economic-social development, this paper explored the driving forces of land use change in the middle reaches of the Yangtze River (MRYR), by using the least square model, spatial lag model, and spatial error model. The results indicated that: (1） The economic-social development stage of the MRYR have undergone two transition processes during 2000-2018. The first was from the primary production stage II to the middle industrialization stage, with slow growth of urbanization and serious outflow of population, the corresponding period was 2000-2010. The second was from the middle industrialization stage to the late industrialization stage, with steady growth of urbanization and continuous return of population, the corresponding period was 2010-2018. （2) In terms of overall characteristics of land use change, the cultivated land and ecological land continued to decrease, the construction land area continued to increase, and the unused land area remained relatively stable during 2000-2018. In terms of process characteristics of land use change in 2000-2010, cultivated land and forest land were transformed into each other. The major changes were that cultivated land was transformed into construction land and water area, and water area was transformed to wetland. In 2010-2018, cultivated land and construction land were transformed to each other, forest land was transformed to construction land and cultivated land, and wetland was transformed to water area. (3） In 2000-2010, topographic index was the sole common driving factor of five main types of land use change. In 2010-2018, topographic index, per capita GDP change, total population change, and distance from main roads became the common driving factors. Therefore, the government should fully consider the main drivers of various types of land use change, as well as their laws of economic-social development and geographical differentiation, so that land use change could be better adapted to regional natural environmental conditions and economic-social development stage.