The Mu Us Desert is an ideal location to study environmental changes during the Late Quaternary, because of its unique characteristics. The Abaoyan (ABY) profile, a typical aeolian-lacustrine profile located at the eastern edge of the desert, was investigated in this study. A basic chronological framework was established based on a combination of radiocarbon dating by accelerator mass spectrometry and in situ sedimentary phase identification. Furthermore, changes in regional chemical weathering intensity since the Holocene were evaluated through comprehensive analysis of the collected samples in terms of grain size, loss on ignition (LOI), chromaticity, geochemical element contents, and soil micromorphology. The results showed that the ABY profile was under the influence of primary and moderate chemical weathering. Regional paleoclimatic environmental changes could be divided into four stages. During Stage I (before 12.6 ka BP; pre-Holocene), the ABY profile was dominated by aeolian sand, showing a coarse average grain size, low LOI, and high chromaticity values, which may have indicated a dry and cold period. During Stage II (12.6-10.3 ka BP; early Holocene), the ABY profile was dominated by lacustrine sediments, indicating a shallow lake water environment with strong chemical weathering and a warm and humid climate. During Stage III (10.3-4.2 ka BP), the profile was dominated by sandy peat deposits with a relatively large proportion of clay particles suggesting that the intensity of chemical weathering was relatively strong in the region during this period and the climate was mainly warm and humid. During Stage IV (after 4.2 ka BP), the sediment was dominated by aeolian sand and secondary loess, the chromaticity increased, the LOI reduced, and the regional chemical weathering intensity was weaker. The change in chemical weathering intensity in this region was inferred to be a positive response to the Holocene East Asian monsoon circulation.