Aeolian deposits on the southeastern Tibetan Plateau (SETP) can provide evidence of how prehistoric humans were influenced by climatic and environmental changes in high-altitude regions. We present the results of multi-proxy analyses of a middle–late Holocene aeolian section in the SETP, together with the probability density of the ages of various cultural sites within and around the study area. Quartz optically stimulated luminescence dating provides a reliable chronology for this section, and analyses of geochemical elements, color and grain size are used to reconstruct the pattern of climate change during the middle–late Holocene. The results suggest a trend of gradually decreasing moisture from the middle Holocene (∼6 ka) onwards, followed by a slight increase at ∼2 ka, which is supported by TraCE-21 ka simulation results. These changes were closely related to variation in the Indian summer monsoon (ISM) caused by decreasing Northern Hemisphere summer insolation and an increase in the Atlantic Meridional Overturning Circulation. The variations in dust activity are inversely related with moisture and there was a significant decrease in dust activity after ∼2 ka. The drought conditions during the 4.2 ka event recorded within the section appear to be a continuation of the trend of middle–late Holocene climatic deterioration, which is superimposed on a weakening trend of the ISM. The permanent human occupation of the study area after ∼2 ka corresponded to an interval of mild and wet climate when dust activity was relatively weak. An observed correlation between the intensity of human activity and dust storms suggests that the enhancement of human activities played a significant role in increasing the occurrence of dust storms. Overall, our results provide new insights into human-environmental interactions in the SETP.