The western margin of the Yangtze Block hosts the giant Upper Yangtze Pb-Zn metallogenic province, with the occurrence of N400 carbonate-hosted Pb-Zn deposits. More than 50% of these deposits are hosted in carbonate rocks of late Ediacaran to early Cambrian age. Although they have attracted great attention over the past two decades, it is still unclear why such carbonate sequences host so many Pb-Zn deposits and the role that the country rocks played during mineralization. The newly-discovered Maliping Pb-Zn deposit (~6 Mt @ 4.18 wt% Pb and 9.18 wt% Zn) is hosted in early Cambrian strata composed of carbonate and phosphate rocks, black shales, as well as evaporite sulfates, of which the carbonate rocks are the direct ore-hosting rocks. Evidence from mineralogy and the concentrations of ore-forming metals indicate that the phosphate rocks played an important role in providing geochemical barriers during Pb-Zn ore formation. Homogenization temperatures of the primary fluid inclusions in sphalerite and quartz range from 185 to 282 °C, and their salinities vary from 3.39 to 17.17 wt% NaCl equiv. The REE and C-O isotopes imply that the hydrothermal carbonates were formed under relatively oxidizing conditions and that the wall rocks were involved in the Pb-Zn mineralization through dissolution. Sulfur isotopic compositions (δ34S = +7.60–+31.79‰) of sulfides reveal that S2− originated from evaporite sulfates within the ore-hosting strata, and that the black shales acted as an important reducing agent during thermo-chemical reduction (TSR). Pb isotopic ratios of galena (206Pb/204Pb = 17.856–17.973, 207Pb/204Pb = 15.668–15.689 and 208Pb/204Pb = 37.953–38.101) are similar to those of Proterozoic basement rocks in the region. This implies that the basement could be the key source of mineralizing metals. Hence, we propose that: (i) The favorable lithological combination of early Cambrian phosphate rocks, black shales, carbonates and evaporites, as well as Proterozoic basement in the area, were responsible for controlling the majority of Pb-Zn deposits in the late Ediacaran-early Cambrian carbonate sequences in the western Yangtze Block; and (ii) the Maliping Pb-Zn deposit resulted from a combination of mineralized fluids, various trap structures and favorable lithologies, of which the fluids were epigenetic with low to moderate temperatures and salinities.