A series of terranes in northwestern Tibet were progressively accreted to the southern margin of the Asian plate during the late Paleozoic to early Cenozoic. Numerous igneous rocks generated in the South Kunlun and Karakul–Mazar terranes help to elucidate the evolution of the northern active continental margin of the Tanymas–Jinshajiang Paleo-Tethys Ocean. In this study, zircon SHRIMP U–Pb data, zircon trace elements, hornblende major and trace elements, whole-rock major and trace elements, whole-rock Sr–Nd isotopes, and zircon Hf isotopes are analyzed to study the age, petrogenesis, and tectonic setting of the Qiate and Bulunkou plutons emplaced in the Karakul–Mazar terrane. Zircon U–Pb dating shows that the Qiate pluton was emplaced at ~ 240 Ma and the Bulunkou pluton at 221–219 Ma. Elemental and isotopic data indicate that the Qiate S-type leucogranite was generated by the partial melting of metasedimentary rocks in the thickened lower continental crust (~ 40–50 km). The Bulunkou I-type granodiorite was likely generated through the reworking of metasedimentary rocks by oxidized mantle-derived mafic magmas in the normal lower continental crust (< 40 km). Because of the injection of the oxidized mantle-derived magmas, the Bulunkou granodiorite is more oxidized than the pure crust-derived Qiate leucogranite. Integrated with previous findings, this study provides new data and interpretations to support that during the Middle–Late Triassic, in response to the northward subduction of the Tanymas–Jinshajiang Paleo-Tethys oceanic slab, the South Kunlun and Karakul–Mazar terranes developed into an active continental margin undergoing crustal thickening and lithospheric delamination.