The thick and continuous Cenozoic successions in the Qaidam Basin provide an excellent paleoclimate archive. Here, we focus on the ostracod fauna, stable isotope records, and paleoweathering indices from a well-dated Cenozoic sedimentary section in the Qaidam Basin, to develop an understanding of Middle Miocene aridification in central Asia. Microfossil analyses suggest that the ostracod species diversity decreased suddenly after 13.3 Ma, and that the dominant ostracod genus shifted from Ilyocypris to Cyprideis. Stable isotope data from ostracod valves have displayed abrupt positive shifts of 3.75‰ in δ18O values and 5.28‰ in δ13C values since 13.3 Ma. The chemical index of weathering (CIW) and K2O/Na2O ratios decrease markedly after 13.3 Ma, reflecting a significant decrease in chemical weathering intensity. These combined and consistent observations suggest that the Qaidam Basin has experienced increased aridification since 13.3 Ma. The dating was obtained directly from previous magnetostratigraphic studies and can be correlated accurately with global climate evolution and regional tectonic events. A comparison of these results with global paleoclimatic records and previous geologic studies of the Tibetan Plateau revealed that global cooling, rather than uplift of the Tibetan Plateau, played a key role in the drying of the Qaidam Basin at approximately 13 Ma.