Spatial optimization of land use is essential to achieve systematic utilization of land resources and sustainable development of the environment and economy. Due to inappropriate land and resource development, and ecological damage resulting from urbanization and industrialization, spatial optimization of land use must take account of ecological constraints. Here, we present an analysis of the Yun-Gui plateau region, which is important because of a shortage of utilizable land and extremely complicated ecological and environmental problems. It illustrates that poorly considered land use decisions will lead to ecological problems. We examined the natural features, ecological background, and socioeconomic development of the Yun-Gui plateau region in order to create an integrated ecological risk evaluation system and model of the major risk factors, including natural disasters, human activity, ecological sensitivity, and critical ecological functions. Additionally, the evaluation system made it possible to perform a comprehensive ecological risk evaluation of land development in the Yun-Gui plateau region.Utilizable land was defined as that with an inclination less than 8°, that accounts to a total area of over 8 km², which is termed the Yun-Gui flatland. A spatial overlay analysis indicated that 21.52% of the area was at high risk, 63.51% at medium risk, and 14.97% at low risk. The high-risk area was mainly in the south of Zhunyi and northeast of Bijie in Guizhou Province. The medium-risk area was concentrated in the south of Guizhou Province, Xishuangbanna, the local area in the south of Puer, and in the valley area of western Yunnan. By contrast, the low-risk area was distributed mostly in the east of west Guizhou and the central eastern region of Yunnan Province. This study focused on bare land with little vegetation, which was regarded as a suitable land for development according to ecological and agricultural criteria. The area of utilizable land was about 3,586 km² of the Yun-Gui flatland, less than 1% of the region's land area. This was mainly located in Chuxiong, Honghe, Qujing, Kunming, and southern Guizhou. In order to ensure the sustainable use of regional land resources, we propose the following recommendations:(1) change the extensive and inefficient use of land to promote the economical and intensive use of flatland; (2) promote industrial projects and urban construction on hillsides according to local conditions; and (3) strengthen ecological and environmental protection while promoting the development and utilization of gently sloping wasteland and avoiding geological disasters with erosion control. This case study on the Yun-Gui plateau region presents an integrated ecological risk assessment method and provides a technical reference for the optimization of land use.