The tectonic evolution of West Kunlun Mountains (WKM), which is located in the NW margin of the Tibetan Plateau, plays an essential role in understanding the source-to-sink relationship between this orogenic belt and SW Tarim Basin. In this study, we conduct an integrated research incorporating detrital zircon UPb geochronology, petrography, and heavy mineral analysis of the Cenozoic synorogenic sediments from Keliyang section, SW Tarim Basin, together with the published data in the WKM forelands, and thus we can discuss the Cenozoic tectonic evolution in this activate tectonic domain. The results suggest that the NW Tibetan Plateau has experienced a four-stage evolution during the Cenozoic, characterized by three notable provenance changes occurring in the late Eocene (∼40 Ma), late Oligocene (∼26 Ma) and latest Miocene-early Pliocene, respectively. In the early Middle Eocene, the Tarim-Tajik basin was still occupied by an epicontinental sea belonging to the Neotethys Sea. Sediments in the forelands were mainly originated from erosion of the residual relief of WKM. By ∼40 Ma, the new additions of sediments from the uplifted Tianshuihai and/or South Kunlun terranes occurred, which can be attributed to the uplift of central Tibet due to the ongoing Indian northward indentation. This scenario was roughly synchronous with the final open marine seawater retreat from the Tarim Basin. We propose that the Cenozoic uplift of the Tianshuihai/South Kunlun terranes may be initiated prior to ∼40 Ma, indicating that the collision-induced deformation has propagated to the southern part of WKM by that time. Since ∼26 Ma, distal deposits increased abruptly, which can be attributed to the outward growth of the Tibetan Plateau and/or regional climate change. Finally, the shift in provenance since the latest Miocene-early Pliocene was related to the intensive uplift of WKM.