The Mesozoic evolution of the Qiangtang Basin in the Tibetan Plateau, which potentially hosts oil and gas resources, is not fully understood, particularly in the context of the opening and closure of the Tethyan oceans. To better understand the tectonic evolution of the Qiangtang Basin and the history of sedimentation, we obtained 788 new U-Pb detrital zircon ages from 12 sandstone samples. Our results show that the provenance of the Mesozoic strata varies both in space and time. In the central part of the basin (Central Qiangtang), older sedimentary rocks are characterized by unimodal age spectra (300–233 Ma) that indicate a proximal arc source. Trace-element compositions of Permian to Triassic zircons from Lower Triassic strata are characteristic of crystallization in arc and backarc environments, thus supporting previous suggestions that the Qiangtang Basin formed as a backarc basin during subduction of the Paleo-Tethys oceanic lithosphere. Younger (Upper Triassic and Jurassic) strata in the Qiangtang Basin received detrital zircons from diverse sources that included Cambrian to Triassic magmatic rocks and Paleozoic strata in the Central Qiangtang, and Triassic flysch deposits in the Songpan-Garze Terrane. We suggest that this change in provenance — from a unimodal arc source that produced zircons in Lower–Middle Triassic rocks to the diverse provenance recognized in the Upper Triassic strata — marks the closure of the Paleo-Tethys Ocean during the Late Triassic. Jurassic sedimentation in the Qiangtang Basin occurred during the expansion of the Meso-Tethys Ocean (Early–Middle Jurassic) and the subsequent subduction of this ocean (since the Callovian). During the Early Cretaceous, the closure of the Meso-Tethys Ocean led to an uplift and a sedimentary hiatus that marked the end of marine sedimentation in the Qiangtang Basin.