Influenced by the far-field effect of the India–Eurasia collision during the Cenozoic, both the Tianshan Range and Kuqa Depression underwent multi-phases of intracontinental tectonic activation. The extremely thick Cenozoic sediments in the Kuqa Depression recorded the basin-mountain coupling process of the South Tianshan and Kuqa Depression. In this study, detailed structural investigations, stratigraphic analysis, and detrital zircon U–Pb dating of the Cenozoic sediments were conducted in the Kuqa Depression to reconstruct the Cenozoic uplift history of the South Tianshan Range. U–Pb ages of detrital zircon from sandstones show four age peaks that correspond to four significant provenance changes in the Kuqa Depression. These four periods of changes occurred at the Cretaceous–Early Cenozoic, Late Eocene–Oligocene, Early Miocene–Middle Miocene, and Early Pliocene–Early Pleistocene. These changes in provenance reflect variations in tectonic activation and paleogeographic settings in the Kuqa Depression–Tianshan Range. Combined with the syn-tectonic growth strata and previously published magnetostratigraphy and low-temperature thermochronology data, we therefore argue that significant Cenozoic deformation and uplift of the Tianshan Range was initiated at the Early Eocene (50–46 Ma), strengthening in the Late Eocene(∼36 Ma), becoming more evident and extending to the entire Tianshan and Basin–Range boundary during the Middle Miocene (13–10 Ma), and culminating and extending to the southern Kuqa Depression since the Early Pliocene (∼6.5 Ma), thus suggesting the continuous convergence of the on-going India–Eurasia collision in the Cenozoic.