The Mesozoic–Cenozoic uplift history of South Tianshan has been reconstructed in many ways using thermochronological analyses for the rocks from the eastern Kuqa Depression. The main difference in the reconstructions concerns the existence and importance of Early Cretaceous and Paleogene tectonic activities, but the existence of a Cenozoic differential uplift in the Kuqa Depression remains enigmatic. Here, we present new apatite fission-track ages obtained for 12 sandstone samples from the well-exposed Early Triassic to Quaternary sequence of the Kapushaliang section in the western Kuqa Depression. The results reveal that there were four pulses of tectonic exhumation, which occurred during the Early Cretaceous (peak ages of 112 and 105 Ma), Late Cretaceous (peak age of 67 Ma), Paleocene–Eocene (peak ages at 60, 53, and 36 Ma), and early Oligocene to late Miocene (central ages spanning 30–11 Ma and peak ages of 23 and 14 Ma), respectively. A review of geochronological and geological evidence from both the western and eastern Kuqa Depression is shown as follows. (1) The major exhumation of South TiansShan during the Early Cretaceous was possibly associated with docking of the Lhasa block with the southern margin of the Eurasian plate. (2) The Late Cretaceous uplift of the range occurred diachronically due to the far-field effects of the Kohistan-Dras Arc and Lhasa block accretion. (3) The Paleogene uplift in South Tianshan initially corresponded to the far-field effects of the India–Eurasia collision. (4) The rapid exhumation in late Cenozoic was driven by the continuous far-field effects of the collision between India and Eurasia plates. The apatite fission-track ages of 14–11 Ma suggest that late Cenozoic exhumation in the western Kuqa Depression prevailed during the middle to late Miocene, markedly later than the late Oligocene to early Miocene activity in the eastern segment. It can be hypothesized that a possible differential uplift in time occurred in the Kuqa Depression during the late Cenozoic.