The temporal and genetic association between Mississippi Valley-type (MVT) Zn–Pb mineralization and hydrothermal dolomitization remains controversial. To determine the origin of hydrothermal dolomite and its genetic links with the MVT ore deposit, detailed petrographic observations and geochemical analyses were conducted on various carbonates from the giant Huize MVT Zn–Pb ore district in SW China. The following paragenetic sequence of the carbonates (from the early to late stages) was established: host limestone (ML), early diagenetic micritic dolostone (D1), late diagenetic or pre-ore fine- to medium-grained ferroan dolostone (D2) and medium- to coarse-crystalline non-ferroan dolostone (D3), pre-ore reworked D3 dolomite (D3o), ore-related void-filling dolomite cement (DC), and calcite cement (CC) related to sulfide mineralization. D2, D3, DC, and CC exhibit higher homogenization temperatures for fluid inclusion than the burial temperature, indicating a hydrothermal origin. Geochemical data indicate that D2, D3, D3o, DC, and CC display oxygen isotope depletion and radiogenic Sr isotope enrichment signatures relative to D1. Their parent fluids have more positive δ18O values and similar or lower δ26Mg values relative to those of D1 and seawater. These geochemical proxies indicate that the pre-ore hydrothermal dolomites (D2 and D3) formed from modified seawater circulated in the underlying sandstone aquifers through fault-related thermal convection. DC and CC, related to Zn–Pb mineralization, were formed by the dissolution and reprecipitation of preexisting carbonates. Sphalerite shows higher temperatures and salinities compared with D2 and D3 dolostones, indicating that the ore-forming fluid, different from the hydrothermal dolomitizing fluid, originated from a deep-sourced brine. In situ U–Pb dating of D3o reveals that the pre-ore hydrothermal dolomitization occurred at 253.7 ± 8.7 Ma, and a late-stage hydrothermal imprint occurred at 203 ± 11 Ma, likely related to tectono-thermal events, including the Emeishan large igneous province and Indosinian Orogeny, respectively. These findings imply that the hydrothermal dolomitization and Zn–Pb mineralization in the Huize ore district are likely associated with the multistage basin and basement fluid flows driven by elevated geothermal gradient and tectonic compression, respectively. The void-filling DC and CC and their cathodoluminescence characteristics are useful indicators for MVT Zn–Pb ore exploration.