The exhumation history and tectonic evolution of the Qilian Shan at the north-eastern margin of the Tibetan Plateau has been widely debated. Here, we present apatite fission-track (AFT) data for 12 Ordovician granodiorite samples along a vertical transect in the eastern Qilian Shan. These thermochronometry data indicate that the eastern Qilian Shan experienced a three-stage cooling history, including: (i) rapid initial cooling in the late Cretaceous; (ii) a stage of quasi isothermal quiescence from ~ 80 to 24 Ma; and (iii) rapid subsequent cooling beginning in the early Miocene. The inferred cooling rates for the three stages are 6.8 ± 4.9 °C Ma−1, 0.6 ± 0.2 °C Ma−1 and 2.7 ± 0.9 °C Ma−1 respectively (±1 σ). Assuming a geothermal gradient of 25 °C km−1, the exhumation rates for the three stages are 0.27 ± 0.20 mm a−1, 0.017 ± 0.007 mm a−1 and 0.11 ± 0.04 mm a−1 respectively (±1 σ). We suggest that the late Cretaceous cooling records collision of the Lhasa block with the Eurasian continent and that the Miocene cooling represents uplift/exhumation of the Qilian Shan.