The middle reaches of the Yangtze River (including Hubei, Hunan, and Jiangxi Provinces) and the "Central Triangle City Group" are located in the center of the Yangtze River Economic Belt and are one of the key national ecological security areas. The land use pattern of this region is not only affected by the local geographical environment and social and economic development but also will be closely associated with the sustainable development of the future social environment. Based on the Landsat TM remote sensing images of 1990, 2000, 2010, and 2015, this study reveals the temporal and spatial patterns of land use change and their relationships with socio-economic factors in the past 25 years by means of landscape pattern analysis, gradient analysis, and correlation analysis. The results showed (1) the cropland and forest land areas were the dominant land types (30% and 50%, respectively), and the proportion of construction land was < 3%. The land use types (forest land, shrub, water body, grassland, and orchard) with important ecological functions accounted for 67%. (2) Along the central city-edge area gradient, each land use type showed obvious spatial characteristics. In particular, the proportions of construction land and cropland areas significantly decreased, the degree of fragmentation increased, while the forest land tended to be integrated. (3) In the past 25 years, cropland and forest land decreased by 1.06% and 0.49%, respectively, and the construction land increased by 1.08%. The degree of regional landscape fragmentation and the landscape diversity increased. Except for forest land, all land use types were significantly related to socio-economic factors (population, urbanization levels, output values of three industry sectors, etc.). These results suggest that, on the one hand, compared with the coastal city group, land use changes in the middle reaches of the Yangtze River have been relatively small, and there is a good basis of land use types for the provision of ecosystem services. On the other hand, there is a great challenge for ecological protection in this region. The main measures are to delineate the red line of ecological protection, protect high-quality cropland, control the scale of urban expansion, strengthen the construction of ecological corridors and ecological nodes, and enhance the ecological functions of regional landscapes in order to meet the needs of sustainable development of the Yangtze River Economic Belt in the future.