The Qaidam Basin, located on the northeastern margin of the Tibetan Plateau, is characterized by a “mountain–deep basin” structural framework and Cenozoic sedimentary fill exceeding 10 km, which has given rise to China’s largest continental saline-lake potash metallogenic belt, containing over 80% of the nation’s proven reserves. Since the Neogene, the basin has undergone multiple phases of tectonic deformation. Under the combined influence of plateau uplift and extreme regional aridification, secondary depressions such as Qarhan, Dalangtan–Heibei, Kunteyi, and Mahai developed, forming a composite mineralization system dominated by brine-type deposits with coexisting solid–liquid mineralization. The potash-forming process is jointly controlled by four-dimensional factors: tectonics, climate, provenance, and sedimentation. Based on a systematic review of tectono-sedimentary evolution and paleoclimate changes, this study reconstructs the spatiotemporal distribution and controlling mechanisms of potash mineralization. The results indicate that tectonic differentiation determined the framework of brine accumulation and storage, climatic aridification drove evaporation concentration and mineralization rhythms, while sustained provenance supply provided sufficient material input. Combined with lithofacies–paleogeographic differentiation, the sedimentary center of the basin migrated repeatedly from the Early Pleistocene to the Holocene. On the basis of integrated analysis of metallogenic factors, the evolution of potash mineralization in the Qaidam Basin can be divided into five stages: unified paleolake subsidence, multi-depression differentiation, extreme aridification and concentration, fault-controlled inheritance and metallogenic climax, and the modern saline-lake cluster. Furthermore, three metallogenic models are identified: central sedimentary-center type, foreland thrust-belt-controlled type, and northwestern tectonically controlled type. This evolutionary sequence and model framework not only reveal the dynamic essence of saline-lake potash mineralization under the uplift of the Tibetan Plateau, but also provide a theoretical basis and practical guidance for deep brine exploration and the refinement of metallogenic models in China.