Abstract Mehdiabad is the world’s largest Mississippi Valley-type (MVT) Zn-Pb deposit (394 million tonnes [Mt] of metal ore at 4.2% Zn, 1.6% Pb) and contains significant barite resources (>40 Mt). Such large accumulations of barite are not common in carbonate-hosted Zn-Pb deposits. Therefore, the origin of the barite and its association with the Zn-Pb mineralization is of significant interest for further investigation. Field work and petrographic studies indicate that the Zn-Pb-Ba orebodies in the Mehdiabad deposit are hosted by Lower Cretaceous carbonate units of the Taft and Abkuh Formations. Fine- to coarse-grained barite with lesser siderite formed in three stages (S1, S2, and S4), along with a quartz-sulfide stage (S3) with minor quartz, sphalerite, galena, chalcopyrite, and pyrite, and the main Zn-Pb sulfide stage (S5) with massive sphalerite and galena. The barites have δ34S values from 17.7 to 20.6‰, δ18O values from 13.2 to 16.8‰, Δ33SV-CDT values from –0.001 to 0.036‰, and initial 87Sr/86Sr ratios from 0.707327 ± 0.000008 to 0.708593 ± 0.000008 (V-CDT = Vienna-Canyon Diablo Troilite). The siderites have δ13CV-PDB values from –3.8 to –2.7‰, and δ18OV-SMOW values from 18.2 to 20.9‰ (V-PDB = Vienna-Pee Dee Belemnite, V-SMOW = Vienna-standard mean ocean water). These geochemical data, and the barite morphology, point to a diagenetic origin for all stages of barite. We suggest that S1 and S2 barite precipitated from pore fluids at the sulfate-methane transition zone in a methane-diffusion-limited environment with increasing methane content. S4 barite precipitated when the methane- and barium-bearing cold-seep fluid migrated to the shallow carbonate sediments and formed a methane-in-excess setting. For the three stages, the SO42- in barite came from the residual SO42- in pore fluids undergoing sulfate-driven anaerobic oxidation of methane, and the Ba2+ came from dissolved biogenic barite and terrigenous materials in the Taft and Sangestan Formations. Primary fluid inclusions trapped in S3 quartz have salinities of 5.6 to 8.1 wt % NaCl equiv and homogenization temperatures of 143.8° to 166.1°C. The quartz has δ18OV-SMOW values ranging from 9.8 to 22.5‰ and δ30Si values from –1.3 to –0.9‰. These data indicate hydrothermal fluid flow occurred between the diagenetic S2 and S4 events. Secondary fluid inclusions with salinities of 17.70 to 19.13 wt % NaCl equiv and homogenization temperatures of 123.0° to 134.0°C are found in the S3 quartz, too. They might represent the hydrothermal event formed by basinal brines in S5. According to the ore textures and the comparison of the sulfur isotopes between S5 Zn-Pb sulfides and the digenetic barites, the barite provided a host and a sulfur source for the later Zn-Pb mineralization. The relationship between barite and the Zn-Pb mineralization indicates that significant accumulations of sulfates may be a critical exploration target for this kind of giant deposit.