Evaporites are of great significance because they provide crucial information on paleoclimate and hydrochemistry. This paper presents a depositional system comprising a mixture of siliciclastics, carbonates, and evaporites that recorded the Eocene sedimentary evolution in the western Qaidam Basin, China, in response to mountain building and climate change. Based on lithology and rock textures, three types of evaporites – thick-bedded halite, macrocrystalline glauberite–anhydrite association and anhydrite lumps – are identified in the Xiaganchaigou Formation (43.8–35.5 Ma). High-frequency superimposed sequences are also identified, with mineral paragenesis successively changing from argillaceous clastics to carbonates to sulfates and chloride. These associations are suggested to have formed during progressive lake salinization and early diagenesis. The results of stable isotopic data and trace element abundances suggest a semi-closed saline lacustrine environment, with intermittent terrigenous sediment and freshwater inputs during humid climatic periods. The transition of evaporitic associations from glauberite–anhydrite to halite associated with the continuous salinization of the lacustrine basin indicates a decrease in moisture transported to the Qaidam Basin due to the global cooling and the initial uplift of the Altyn Mountains in the Eocene.