Development of urban human settlement environments (HSEs) is an integral part of promoting high-quality and sustainable regional development and constructing a beautiful China. The city of Lanzhou, located at the geometric center of China, is the only provincial capital traversed by the Yellow River. Given the constraints posed by the valley topography and the need for economic development, the development of this HSE, which is located within an arid region, poses considerable challenges. Evidently, an understanding of the evolution of HSEs and drivers of changes in them contributes to high-quality, sustainable urban development in arid and semi-arid regions. An analytical model was developed using the parameters of relief degree of land surface, human comfort days, the land cover index, nighttime light index, and precipitation. This model was used in combination with population density and the gross domestic product to analyze the spatial distribution of Lanzhou's HSE and its drivers. The results showed that landscapes in Lanzhou underwent significant changes between 2000 and 2022, with an increase in building-up land (+0.946%), cultivated land (+0.134%), and forest land (+0.018%) and a decrease in grassland (−1.10%). There was significant outward expansion of the main urban zone of Lanzhou and of various county towns, with the increase in building-up land being most prominent. During this period, there were significant changes in the periphery of the core urban area and county towns in Lanzhou, with decreases moving from the urban center (the highest value) to the surrounding areas (Yongdeng County had the lowest value). The correlation between the HSE and population density grew stronger in Anning and Chengguan Districts but became weaker in Xigu and Qilihe Districts. Spatiotemporal variations in the HSE were primarily caused by climate change, followed by human activities, and were also influenced by the valley topography. Overall, the spatial distribution of population density and the HSE in Lanzhou demonstrated good consistency under the influence of economic development and urbanization.
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