Situated in the northwestern Qinghai-Tibet Plateau, the Qaidam Basin is the largest Cenozoic terrestrial intermountain (enclosed) basin in the world. It is an ideal place for understanding the coupling control of tectonics and climate on sedimentary evolution. Numerous studies on the Quaternary sedimentary evolution of the Qaidam Basin have been done, most of which are local, conceptual, and qualitative in nature. We have investigated the entire Qaidam Basin and its surrounding mountains quantitatively as a single entity to probe the Quaternary evolution of the basin-range system in the northern Qinghai-Tibet Plateau. We used a basin and landscape dynamics (Badlands) modeling algorithm that is capable of modeling landscape evolution by simulating erosion, sediment transport, and deposition in a source-to-sink context by considering climate changes and tectonic uplift/subsidence. We have simulated the evolution of the Qaidam Basin and its surrounding mountains since 2.5 Ma quantitatively. Tectonic uplift and climate changes appear to have a direct impact on the denudation and deposition rates, but the impact varies through time. The deposition in the Qaidam Basin was mainly affected by tectonic movement during the period of 2.5–0.6 Ma, reaching a maximum deposition thickness of 2130 m at the end of 0.6 Ma, which was prevailed by climate after 0.6 Ma during the last four glacial-interglacial periods, reaching a maximum deposition thickness of 3200 m. The Qilian Mountains and the Kunlun Mountains contributed the bulk sediments to the Qaidam Basin of approximately 35% and 40%, respectively. The Altun Mountains made a significant contribution to the sediments in the Qaidam Basin during the early period of the Quaternary from 2.5 to 2.4 Ma due to a high denudation rate. The findings provide new insights for analyzing geomorphic and landscape evolution as well as source-to-sink systems in the Northern Qinghai-Tibet Plateau or elsewhere.