The Maoping carbonate-hosted Pb-Zn deposit (25 Mt ores @ 12–35% Zn + Pb) is a representative and the third-largest Pb-Zn deposit in the Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province (SYGMP). In this study, Pb-Zn-Cd isotope analyses were performed on sphalerite from Maoping, in order to understand the ore metal source and metallogenesis in the SYGMP. The sphalerite samples have narrow ranges of Pb isotope ratios: ²⁰⁶Pb/²⁰⁴Pb = 18.675–18.751, ²⁰⁷Pb/²⁰⁴Pb = 15.758–15.768, and ²⁰⁸Pb/²⁰⁴Pb = 39.287–38.436. This implies thorough mixing of two Pb sources, which we interpreted to be the Devonian-Carboniferous ore-hosting carbonate wallrocks and the Neoproterozoic Kunyang/Huili Group (Gp.) clastic and metamorphic rocks. The Maoping sphalerite samples have uniform δ⁶⁶Zn (−80.07 to + 0.25‰) and δ¹¹⁴Cd (−0.10 to + 0.27‰) values, which further support complete source mixing. In the δ⁶⁶Zn vs. Cd/Zn plot, the Maoping sphalerite data fall close to the field of basement rocks and distal to the carbonate wallrocks, indicating that the ore zinc was mainly derived from the metamorphic basement with heavier δ⁶⁶Zn values and low Cd/Zn ratios with certain contributions from the minor carbonate wallrock with lower δ⁶⁶Zn values and high Cd/Zn ratios. In the δ¹¹⁴Cd vs. 1/Cd plot, all Maoping sphalerite samples fall inside the Mississippi Valley-type (MVT) field, and the deposit shares many geological and sulfide geochemical (incl. isotopic) features with MVT deposits. Thus, the Maoping Pb-Zn mineralization is best classified as MVT, and the sulfide precipitation in structural (fault-fold) traps was caused by binary mixing of a metal-bearing and a reduced S-bearing fluid.