The Laoliwan Ag-Pb-Zn deposit is situated in the southern margin of the North China Craton and represents the first large-scale Ag-Pb-Zn ore deposit discovered in the Xiaoshan District. Ag-Pb-Zn orebodies are structurally controlled by NW- and NNW-trending faults and primarily hosted within early Cretaceous granite porphyry intrusions. In this study, sulfide Rb-Sr isotope dating and C-H-O-S-Pb multiple isotope compositions were conducted to constrain the ore genesis of this deposit. The Rb-Sr isotopic data of sulfides yield a weighted mean isochron age of 132.8 ± 9.5 Ma and an initial ⁸⁷Sr/⁸⁶Sr ratio of 0.7115 ± 0.00016, indicating that mineralization occurred during the early Cretaceous and the ore-forming materials were derived from a crust–mantle mixed reservoir. The δ¹³ C (−1.3‰ to 0.7‰), δD (−96.3‰ to −86.7‰) and δ¹⁸O_H2O (0.3‰ to 5.6‰) values suggest that the ore-forming fluids were mainly derived from magmatic water with a contribution of meteoric water during mineralization. The δ³⁴S values of sulfides (+2.0‰ to +5.8‰) indicate a magmatic source. The Pb isotope data (²⁰⁶Pb/²⁰⁴Pb = 17.301–17.892, ²⁰⁷Pb/²⁰⁴Pb = 15.498–15.560, ²⁰⁸Pb/²⁰⁴Pb = 37.873–38.029) also reveal that the ore-forming materials originated from the lower crust with a small amount from the mantle source. By integrating geochronological and geochemical data, this study proposes that the Laoliwan Ag-Pb-Zn deposit is characterized as an epithermal deposit, with potential for the discovery of concealed porphyry Cu-Mo mineralization at depth. It is inferred to be related to tectonic–magmatic–fluid activities in the context of early Cretaceous lithospheric thinning along the southern margin of the North China Craton.