The Duobagou Permian–Triassic granites of the Dunhuang orogenic belt are of great importance in understanding the tectonic evolution of the southernmost Central Asian Orogenic Belt. LA-ICP-MS U–Pb zircon ages indicate that Permian–Triassic granitic intrusions from the Duobagou area formed at 276–274 Ma and 246 ± 1 Ma. These granites have high SiO2, Na2O and K2O, but low Al2O3, CaO and MgO contents and belong mainly to the high-K calc-alkaline I-type granite series. Based on whole-rock geochemistry and Sr–Nd and zircon Hf isotopes, the Duobagou Permian–Triassic granites were dominantly derived from the partial melting of lower continental crust formed during late Palaeoproterozoic to Mesoproterozoic times in a post-collisional extensional setting. Permian granites with zircon ϵHf(t) values of −5.4 to +3.1 and Hf model ages of TDM2 = 1.14–1.70 Ga indicate the involvement of a mantle component in their petrogenesis. Triassic granites with higher zircon ϵHf(t) values (+0.5 to +3.8) and TDM2 = 1.08–1.31 Ga suggest more juvenile sources caused by a greater contribution of mantle-derived melts, indicating a significant crustal growth. Regional extension from lithospheric delamination and heating from asthenospheric upwelling were proposed to have triggered the partial melting of lower crust, resulting in the generation of the Permian–Triassic magmatism. This may have been the mechanism for the significant crustal growth during Permian and Triassic times in the southernmost Central Asian Orogenic Belt.