The Gangjiang Cu–Mo deposit is located in the central Gangdese porphyry Cu belt (GPCB), south Tibet. Geological investigation reveals that the Gangjiang deposit is characterized by early potassic alteration, followed by late phyllic and argillic alteration. Late alteration has different degrees of overprinting over the potassic alteration zone. Copper-Mo orebodies are predominantly hosted in the potassic and phyllic alteration zones of the Miocene monzogranite porphyry (MGP) and granodiorite porphyry (GDP). In this study, we present the chemistry and Sr–Nd–Pb–Hf–O isotope compositions of fertile MGP and GDP, barren tonalite porphyrite (TP), and microgranular mafic enclaves (MMEs). Chemical compositions indicate that these intrusions are I-type granites that show high–K calc-alkaline signatures. The negative correlation between Dy/Yb and SiO2 indicates that the intrusions experienced fractionation of amphibole. They have high Sr/Y (>70) and La/Yb (>38) ratios, strong negative Nb–Ta–Ti anomalies, and positive Pb anomalies are typical for arc magma. The high Mg# of various porphyry intrusions (43–65) and MMEs (47–58) indicate the input of mafic components. Various intrusions have whole-rock 87Sr/86Sr(t=13Ma) ratios of 0.70529 to 0.70674, negative εNd(t=13Ma) (−5.0 to −1.2), positive zircon εHf(t) (1.2–9.8), and homogeneous δ18O (5.8–7.1 ‰, mean 6.6 ‰). The MMEs have similar Sr–Nd–Pb–Hf–O isotopic compositions with their host rocks. The features reveal that the Gangjiang adakite-like intrusions and MME samples were derived from the partial melting of the Lhasa Paleoproterozoic crust, with contributions from the juvenile mantle that has been metasomatized by subducted sediments-derived melts. Note, the MGP, GDP, and two types of MMEs have slightly lower δ18O values (down to 4.76 ‰) but higher εNd(t) (up to −1.2) than barren TP, indicating their formation involves more mantle components. Furthermore, the MMEs in the TP and MGP have high Cu contents (up to 1485 ppm), similar to the phenomenon occurs in the Qulong deposit. The Cu-rich MME is probably formed by Cu-refertilization by the underplate arc magma in the juvenile crust. The εHf(t) and εNd(t) values of fertile porphyries increased from the Jiru, Gangjiang, to Qulong deposit indicating increased mantle material additions from the west to the east section of the GPCB. These variations in mantle components have led to an increase in the size of the porphyry Cu deposits from Jiru to Gangjiang, and then to Qulong.