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• Clay-sized geochemistry reveals the Qaidam Basin (QB) Paleogene weathering history. • QB Paleogene silicate weathering intensity presents a continuously decreasing trend. • Global cooling was the main regulator of Paleogene chemical weathering processes. • Clay-sized geochemical indices aptly reveal weathering histories in coarse sediment. An integrated multiproxy dataset involving both mineralogical and geochemical investigations of the northern Tibetan Plateau helps in assessing regional weathering processes linked to topographic evolution and environmental change. However, changes in landscape and drainage reorganizations caused by active tectonics and remarkable climate change during the Cenozoic characterize the basins in and around the Tibetan Plateau by frequent facies changes and coarse lithologies, which largely limit the reliability of bulk geochemical indicators for revealing the regional weathering history. Here, we present detailed geochemical investigations of clay-sized sediments collected from the Hongliugou section (54–26 Ma) in the northern Qaidam Basin to reconstruct high-resolution chemical weathering records of the northern Tibetan Plateau. To prevent chlorite bias when calculating the chemical index of alteration (CIA) in the clay-sized sediments, we propose a modified CIA formula (CIA Mg+), in which Mg is added as a soluble cation that can be removed during weathering, similar to Na, K and Ca; thus, CIA Mg+ = Al 2 O 3 /(Al 2 O 3 + Na 2 O + K 2 O + CaO* + MgO) × 100. The CIA Mg+ and illite chemistry indices are generally the highest values in the early Eocene Climate Optimum (∼52–49.5 Ma) and a long-term decreasing trend is present from ∼ 49.5–26 Ma; the Mg/Al ratios of the clay-sized sediments and hydrochloric acid leachates are the lowest during the EECO and present a long-term increasing trend in the following 49.5–26 Ma, thus collectively indicating a continuous decrease in the regional chemical weathering intensity. The weakening weathering process during the Paleogene is mainly attributed to the decreasing global temperature and decline in precipitation caused by global cooling. Our study suggests that the proposed geochemical index based on clay-sized sediments can serve as an efficient proxy for regional chemical weathering reconstruction, even in thick sedimentary sequences with frequently changing facies and lithology. [ABSTRACT FROM AUTHOR]