New-type metasedimentary rock-hosted stratiform Cu deposits occur in the Jianglang Dome. They are hosted by the Late Neoproterozoic Liwu Group and were unusually induced by an epigenetic magmatic-hydrothermal system. However, the source characteristics of fluids and metals remain poorly understood. Here, we employed Re-Os dating and He-Ar-S-Pb isotopes to determine their mineralization age and origin. Chalcopyrite Re-Os isotopic dating defines an isochron age of 162.7 ± 3.2 Ma and a crust-like initial 187Os/188Os ratio of 1.421 ± 0.021 (n = 4). Sulphide He-Ar isotope (n = 20) yields low R/Ra ratios of 0.052–0.144, high 40Ar/36Ar ratios of 479–2463 and low 40Ar*/4He ratios of 0.013–0.804, with calculated Hemantle values of 0.69–2.20 wt.%. In situ chalcopyrite sulphur isotope exhibits positive δ34SV-CDT values of 3.87–9.50‰ (n = 72). Together with similar lead isotope data of chalcopyrite separates (n = 40) and ca. 164 Ma granites (n = 4), as well as low residual gravity anomalies in this region, our integrated data indicate an epigenetic magmatic-hydrothermal mineralization at ca. 163 Ma. The ore-forming fluids were dominantly crust-derived, with minor air-saturated water and negligible mantle input (0.69–2.20 wt.%). This is most likely attributed to the low proportion (total <5 vol%) of sandwiched metabasic rocks in the metalliferous Liwu Group. All the investigated orebodies show source homogeneity, in contrast to classic sediment-hosted stratiform Cu deposits with isotopic heterogeneity. Further, our findings imply significant mineral exploration potential in the Jianglang Dome and analogous domes in the eastern Songpan-Ganze Orogen.