The western Kunlun orogen in the northwest Tibet Plateau is related to subduction and collision of Proto- and Paleo-Tethys from early Paleozoic to early Mesozoic. This paper presents new LA-ICPMS zircon U-Pb ages and Lu-Hf isotopes, whole-rock major and trace elements, and Sr–Nd isotopes of two Ordovician granitoid plutons (466–455 Ma) and their Silurian mafic dikes (~436 Ma) in the western Kunlun orogen. These granitoids show peraluminous high-K calc-alkaline characteristics, with (87Sr/86Sr)i value of 0.7129–0.7224, εNd(t) values of ?9.3 to ?7.0 and zircon εHf(t) values of ?17.3 to ?0.2, indicating that they were formed by partial melting of ancient lower-crust (metaigneous rocks mixed with metasedimentary rocks) with some mantle materials in response to subduction of the Proto-Tethyan Ocean and following collision. The Silurian mafic dikes were considered to have been derived from a low degree of partial melting of primary mafic magma. These mafic dikes show initial 87Sr/86Sr ratios of 0.7101–0.7152 and εNd(t) values of ?3.8 to ?3.4 and zircon εHf(t) values of ?8.8 to ?4.9, indicating that they were derived from enriched mantle in response to post-collisional slab break-off. Combined with regional geology, our new data provide valuable insight into late evolution of the Proto-Tethys.