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Cultural Heritage Sites (CHS) serve as tangible evidence of regional human–environment interactions and spatial representation of historical memory. The research developed a Xinjiang CHS database and integrated geographic information technology and historical geography research methods to examine the spatio-temporal distribution evolution characteristics and geographic influencing factors in the arid region. It utilized the nearest neighbor index, kernel density estimation, the center of gravity model, and standard deviation ellipse to explore the spatio-temporal evolution law. Furthermore, it employed spatial overlay and qualitative text to analyze the geographical influence mechanism of the CHS. The results showed the following: (1) The CHS spatial distribution showed a pattern of “multicore agglomeration-linear extension”, concentrated in 13 key cities and four major areas that extended along the Silk Road routes. (2) The CHS diachronic development fluctuated in a pattern of “three peaks and three valleys”. The spatial center of gravity has shifted from southern Xinjiang to northern Xinjiang, manifesting a concentrated-diffused characteristic along the northeast–southwest axis. (3) The spatial selection followed the rules of “preferring lower terrain” and “proximity to water”. The elevation distribution of CHS has shifted from mid-high elevations to low elevations. The proportion of CHS on low-slope terrain increased from 78.6% in the Pre–Qin period to 93.02% in Modern History. 93.02% of CHS in Modern History were distributed within the 10 km buffer zone of rivers. (4) Climate aridity and human activities formed a dynamic influence mechanism; natural factors constructed the base pattern of CHS distribution, and human activities drove the dynamic adjustment. The findings revealed the historical trajectory and driving logic of the evolution of CHS in Xinjiang and provided a scientific basis for cultural heritage protection and ecological governance. This study had limitations in terms of the limited research scope and the lack of comprehensive quantitative analysis of influencing factors.
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