Understanding the source to sink relationship through time between the Eastern Kunlun Range, one of the major mountain belts in the northern Tibetan Plateau, and the actively deforming Qaidam Basin to the north has important implications for unravelling the growth history of the Tibetan Plateau. In this study, U-Pb dating (laser-ablation–inductively coupled plasma–mass spectrometry) of detrital zircons from 22 sandstone samples (Paleocene to Holocene) collected from four sections within the southwestern Qaidam Basin is combined with provenance analysis and new seismic profile interpretation to investigate the mountain building of the Eastern Kunlun Range and its effects on the development of the Qaidam Basin. The U-Pb age distributions of detrital grains from Paleocene strata are characterized by a major component of Paleozoic to late Proterozoic ages. Furthermore, carbonate debris containing foraminifera have been recognized in the Paleocene conglomerate sequences. We thus suggest that the Eastern Kunlun Range was already exhumed prior to the Paleocene. The southward onlaps of Paleocene to Oligocene strata observed on seismic profiles and the appearance of a Mesozoic component in the detrital zircon age spectra of Eocene to Oligocene strata indicate that the Qaidam Basin was widening southward during that early Cenozoic period. Well-developed post-Oligocene growth strata and the increasing proportion of Mesozoic and Paleozoic U-Pb ages in detrital zircon grains from late Neogene strata demonstrate that the relief of the Eastern Kunlun and Altyn Tagh Ranges increased, leading to isolation and narrowing of the Qaidam Basin, from Miocene to the present. The inferred pulsed deformation in the Eastern Kunlun Range highlights the complex growth history of the Tibetan Plateau.