Based on the oil and gas exploration in western depression of the Qaidam Basin, NW China, combined with the geochemical, seismic, logging and drilling data, the basic geological conditions, oil and gas distribution characteristics, reservoir-forming dynamics, and hydrocarbon accumulation model of the Paleogene whole petroleum system (WPS) in the western depression of the Qaidam Basin are systematically studied. A globally unique ultra-thick mountain-style WPS is found in the western depression of the Qaidam Basin. Around the source rocks of the upper member of the Paleogene Lower Ganchaigou Formation, the structural reservoir, lithological reservoir, shale oil and shale gas are laterally distributed in an orderly manner and vertically overlapped from the edge to the central part of the lake basin. The Paleogene WPS in the western depression of the Qaidam Basin is believed unique in three aspects. First, the source rocks with low organic matter abundance are characterized by low carbon and rich hydrogen, showing a strong hydrocarbon generating capacity per unit mass of organic carbon. Second, the saline lake basinal deposits are ultra-thick, with mixed deposits dominating the center of the depression, and strong vertical and lateral heterogeneity of lithofacies and storage spaces. Third, the strong transformation induced by strike-slip compression during the Himalayan resulted in the heterogeneous enrichment of oil and gas in the mountain-style WPS. As a result of the coordinated evolution of source-reservoir-caprock assemblage and conducting system, the Paleogene WPS has the characteristics of “whole process” hydrocarbon generation of source rocks which are low-carbon and hydrogen-rich, “whole depression” ultra-thick reservoir sedimentation, “all direction” hydrocarbon adjustment by strike-slip compressional fault, and “whole succession” distribution of conventional and unconventional oil and gas. Due to the severe Himalayan tectonic movement, the western depression of the Qaidam Basin evolved from depression to uplift. Shale oil is widely distributed in the central lacustrine basin. In the sedimentary system deeper than 2 000 m, oil and gas are continuous in the laminated limy-dolomites within the source rocks and the alga limestones neighboring the source kitchen, with intercrystalline pores, lamina fractures in dolomites and fault-dissolution bodies serving as the effective storage space. All these findings are helpful to supplement and expand the WPS theory in the continental lake basins in China, and provide theoretical guidance and technical support for oil and gas exploration in the Qaidam Basin.