The Cenozoic deformation history of the Qilian Shan, which is a reactivated fold-thrust belt in the northeastern region of the Tibetan Plateau, is poorly understood but features prominently in the geodynamic mechanism of the evolution of the plateau. The northeastern Qaidam Basin, which is located on the south flank of the Qilian Shan, provides a valuable record of the timing and pattern of the Cenozoic deformation of the Qilian Shan in its synorogenic sediments. This study analyzes the apatite fission-track (AFT) thermochronological signatures of the middle Miocene-Quaternary detrital sediments in the northeastern Qaidam Basin and modern stream sands draining the Qilian Shan as a proxy for the timing of tectonic deformation in the Qilian Shan. Our detrital AFT ages indicate that a Cenozoic initial rapid exhumation event occurred in the Qilian Shan in the late Paleocene-early Eocene (~60–54 Ma), followed by another rapid exhumation event during the middle-late Eocene (~42–38 Ma) and some exhumation during the Oligocene-middle Miocene (~33–14 Ma). Distinct changes in detrital AFT ages at depositional ages of ~12 Ma and ~2.1 Ma suggest that further tectonic deformation affected the Qilian Shan at these times. Our results, along with those of previous studies, suggest that tectonic deformation propagated into the northeastern edge of the Tibetan Plateau almost simultaneously with the India-Asia collision. The spatial evolution of Cenozoic deformation in the Qilian Shan is likely based on the distribution of weak structures in the upper crust.