The Sanjiang Orogen in the Southeastern Qinghai–Tibet Plateau is an ideal region to investigate the geodynamic processes related to the evolution of the Paleo-Tethys Ocean. New zircon SHRIMP U–Pb age data, whole-rock major and trace elements, and zircon Hf–O isotopic data of granodiorites and the associated dioritic enclaves from Baimaxueshan pluton in the eastern margin of the Qamdo–Simao Terrane provide key evidence for the subduction products of the Paleo-Tethyan oceanic lithosphere. Zircon U–Pb ages indicate that the dioritic enclaves and their host granodiorites were synchronously emplaced at ~255 Ma. The host granodiorites are normal calc-alkaline I-type granitoids, and characterized by uniform zircon εHf(t) values (−6.7 to +1.5), a wide-ranging δ18O values (6.1 to 9.3‰), and negative whole-rock εNd(t) values (−7.3 to −5.8). We suggest that these rocks were derived from the partial melting of ancient mafic lower crust with varying contributions from mantle-derived components. The dioritic enclave samples yield εHf(t) values (−4.7 to +2.1) and δ18O (5.8 to 8.3‰), which are similar to those of the host granitoids. They most likely originated from magma mixing between mantle-derived and crust-derived melts at or close to the Moho. The similar emplacement age but distinct whole-rock εNd(t) values between the Lancangjiang arc-related andesites and granodiorites and Baimaxueshan pluton preclude the possibility that they were generated by the same magmatic source. However, the consistent emplacement ages and whole-rock εNd(t) values of the Jinshajiang subduction-related granites and Baimaxueshan granitoids suggested that they were both generated by the westward subduction of the Jinshajiang PaleoTethyan oceanic lithosphere.