The ages of Zn-Pb deposits are exceptionally challenging to determine owing to the lack of suitable mineral chronometers and techniques. Here we present the first result for in situ LA-ICP-MS U-Pb dating of carbonates and barite from a Mississippi Valley– type (MVT) Zn-Pb deposit in South China. Hydrothermal dolomite in close textural and paragenetic association with Zn-Pb sulfides, and calcite and barite cement from the breccia ores, yield ages of 473.4 ± 2.7 Ma and 368.7 ± 3.1 Ma, respectively. Together with new in situ S-Pb-Sr isotope values, these data reveal an epigenetic Zn-Pb mineralization history, agreeing well with a model involving basinal brine accumulation and MVT Zn-Pb sulfide precipitation. Because carbonate is a common mineral in Zn-Pb deposits worldwide, and other minerals in such deposits suitable for isotope dating are generally absent, in situ U-Pb dating of gangue carbonates opens a new window for better defining the ore genesis of this globally important Zn-Pb deposit type and for tracking hydrothermal fluid flow in sedimentary basins.