Both Pb-Zn and Au mineralization can simultaneously occur at the deposit, camp or regional scale, but their spatial-temporal and genetic relationships have received less attention so far. Here we present detailed field investigations and S-Pb-He-Ar isotope data for the Laoyachao deposit, South China, to interpret the intrinsic associations between Pb-Zn and Au mineralization. Both Pb-Zn and Au ores in the studied area are distributed independently but spatially associated with the same granodiorite. Field and microscopic observations, together with previous dating, show that the Au mineralization postdated the Pb-Zn mineralization. The relatively restricted range and lower δ³⁴S values for the Au ores (−0.72 to +0.94 ‰) and the Pb-Zn ores (−1.98 to +2.36 ‰) indicate that both metal mineralization types are attributed to a homogeneous magmatic sulfur source. Lead isotope compositions for the ores and the feldspars from the granodiorites define a well-defined linear array, with the Au ores displaying less radiogenic Pb. In addition, the Pb-Zn ores exhibit lower ³He/⁴He and ⁴⁰Ar/³⁶Ar ratios (0.01–0.26 Ra, 298–313) than the Au ores (0.16–2.93 Ra, 341–382). All evidence demonstrated that, besides the granodiorite end-member, an end-member with high-radiogenic Pb and lower ³He/⁴He values participated in the early Pb-Zn mineralization, in contrast, the other end-member with less radiogenic Pb and higher ³He/⁴He values was involved in the late Au mineralization. Considering that both Pb-Zn and Au mineralization in the studied deposit are spatially, temporally and genetically related to the same granodiorite, the Pb-Zn mineralization associated with granodiorite can provide an indicator for gold exploration.