The active left-slip Altyn Tagh fault defines the northern edge of the Tibetan plateau. To determine its deformation history we conducted integrated research on Cenozoic stratigraphic sections in the southern part of the Tarim Basin. Fission-track ages of detrital apatites, existing biostratigraphic data, and magnetostratigraphic analysis were used to establish chronostratigraphy, whereas composition of sandstone and coarse clastic sedimentary rocks was used to determine the unroofing history of the source region. Much of the detrital grains in our measured sections can be correlated with uplifted sides of major thrusts or transpressional faults, implying a temporal link between sedimentation and deformation. The results of our studies, together with existing stratigraphic data from the Qaidam Basin and the Hexi Corridor, suggest that crustal thickening in northern Tibet began prior to 46 Ma for the western Kunlun Shan thrust belt, at ca. 49 Ma for the Qimen Tagh and North Qaidam thrust systems bounding the north and south margins of the Qaidam Basin, and prior to ca. 33 Ma for the Nan Shan thrust belt. These ages suggest that deformation front reached northern Tibet only ∼10 ± 5 m.y. after the initial collision of India with Asia at 65–55 Ma. Because the aforementioned thrust systems are either termination structures or branching faults of the Altyn Tagh left-slip system, the Altyn Tagh fault must have been active since ca. 49 Ma. The Altyn Tagh Range between the Tarim Basin and the Altyn Tagh fault has been a long-lived topographic high since at least the early Oligocene or possibly late Eocene. This range has shed sediments into both the Tarim and Qaidam Basins while being offset by the Altyn Tagh fault. Its continuous motion has made the range act as a sliding door, which eventually closed the outlets of westward-flowing drainages in the Qaidam Basin. This process has caused large amounts of Oligocene–Miocene sediments to be trapped in the Qaidam Basin. The estimated total slip of 470 ± 70 km and the initiation age of 49 Ma yield an average slip rate along the Altyn Tagh fault of 9 ± 2 mm/yr, remarkably similar to the rates determined by GPS (Global Positioning System) surveys. This result implies that geologic deformation rates are steady state over millions of years during continental collision.