Abstract: The natural environment of human settlements is the ecological basis of people’s production and life. The spatial distribution and core degree of urban built-up areas can reflect the scale and trend of urban development. Exploring the coupling relationship between the two will help promote the simultaneous coordination of urban development and environmental protection. Based on the remote sensing images and other multi-source data of Jinsha River Basin in Yunnan Province in 2010,2015 and 2020, from the perspective of coordinated and sustainable development of city and nature, the urban coreness index is calculated by multi-index fusion, and the human settlements’ natural environment quality index is calculated by multi-method combination. The core degree index of urban built-up area is extracted by threshold segmentation, and the coupling coordination degree model between the core degree of urban built-up area and the quality of human settlements natural environment is further constructed. The coupling coordination degree and development difference degree of the two are calculated. The urban built-up areas in the basin are divided into nine types, and their differentiation rules are revealed from the two dimensions of time and space. The results show that:(1) The coreness index of watershed cities shows a slight downward trend as a whole, and the high-value range of core degree gradually expands with time. Human settlements’ natural environment quality index rose slowly, especially in the middle reaches of the central Yunnan region.(2) There is a strong spatial correlation between the core degree of urban built-up area and the quality of human settlements natural environment, and the coupling degree is higher than 0.8 over the years.(3) The coupling coordination degree of the two shows core city>periphery city, southern city>northern city, central city>eastern and western city, showing the distribution pattern of ‘high in the middle, low around’; the overall coordination degree decreased slightly, and the high coordination range expanded significantly over time.(4) The differences in regional nature, resources and policies have affected the balance between urban development and ecological environment, making the basin cities mainly appear in five types of coupling and coordinated development. The research results provide a scientific basis for the rational development of urban built-up areas and the protection of the natural environment in the basin. The urban coreness index and the human settlements’ natural environment quality index model obtained to provide a reference for similar research.