As urbanization accelerates, characteristics of urban spatial expansion play a significant role in the future utilization of land resources, the protection of the ecological environment, and the coordinated development of population and land. In this study, Yunnan and Guizhou provinces were selected as the study area, and the 2013–2021 National Polar-Orbiting Partnership’s Visible Infrared Imaging Radiometer Suite (NPP-VIIRS) nighttime light (NTL) data were utilized for spatial and temporal change analysis of urban built-up areas. Firstly, the built-up areas in Yunnan and Guizhou provinces were extracted through ENUI (Enhanced Nighttime Lighting Urban Index) indices, and then the urban expansion speed and urban center of gravity migration were constructed and used to explore and analyze the spatial and temporal change and expansion characteristics of built-up areas in Yunnan and Guizhou provinces. The results showed the following. (1) Due to the complementarity between data types, such as NTL, EVI, NDBI, and NDWI, ENUI has better performance in expressing urban characteristics. (2) Influenced by national and local policies, such as “One Belt, One Road”, transportation infrastructure construction, geographic location, the historical background, and other factors, the urban expansion rate of Yunnan and Guizhou provinces in general showed a continuous advancement from 2013 to 2021, and there were three years in which the expansion rate was positive. (3) The center of gravity migration distance of most cities in Guizhou Province shows a trend of increasing and then decreasing, while the center of gravity migration distance in Yunnan Province shows a trend of continuous decrease in general. From the perspective of migration direction, Guizhou Province has the largest number of migrations to the northeast, while Yunnan Province has the largest number of migrations to the southeast. (4) Influenced by policy, economy, population, geography, and other factors, urban compactness in Yunnan and Guizhou provinces continued to grow from 2013 to 2021. The results of this study can help us better understand urbanization in western China, reveal the urban expansion patterns and spatial characteristics of Yunnan and Guizhou provinces, and provide valuable references for development planning and policymaking in Yunnan and Guizhou provinces.