Since the late Miocene, the global climate has experienced a significant cooling. The transition from unipolar to bipolar permanent ice caps was accompanied by rapid cooling and tectonic uplift and ecological transformations. Due to its location at the confluence of the East Asian monsoon, the westerlies, and the Tibetan Plateau alpine zone, the Qaidam Basin is very sensitive to paleoclimatic fluctuations. To understand the process of late Cenozoic paleoclimate change in the eastern Qaidam Basin, a total of 103 mudstone samples were selected from well T1 in the Sanhu Depression. By analyzing the major/trace elements and n-alkanes, the correlation indicators of the major/trace elements and n-alkanes consistently show a trend of increasing aridity during the ShangyoushashanQigequan Formation in the Sanhu Depression of the Qaidam Basin. The results indicate that the paleoclimatic changes during this period were primarily caused by global climate cooling. However, the effects of the Asian monsoon or the uplift of the Tibetan Plateau were superimposed at different stages, resulting in different paleoclimatic characteristics. This study highlights the interplay between global climate forcing and regional tectonic drivers in shaping aridification patterns, providing critical insights into the complex climatic evolution of Central Asia under late Cenozoic cooling.