Calcite is the main gangue mineral in antimony (Sb) deposits, and its compositions can reflect the physicochemical conditions of Sb mineralization. The Yangla is the largest Sb deposit (10 kt Sb @ 14.87 %) in the Jinshajiang suture zone (SW China), and the lode-type Sb orebodies are stratabound or developed along NE-trending fracture zones in marble. To constrain the time of Sb mineralization and establish any genetic link with the local magmatism and wallrocks, we performed calcite Sm-Nd dating and bulk C-O and in-situ Sr isotope analyses. The results show that the Sb mineralization (∼155 Ma) was considerably younger than the Cu-Pb-Zn mineralization (∼230 Ma), skarn alteration (∼234 Ma), and granitoid emplacement (∼230 Ma) at Yangla, but much older than the local W mineralization (∼30 Ma). The initial 87Sr/86Sr ratio of calcite (0.71972–0.72208) is much higher than that of the Triassic granodiorite (0.71149– 0.71990) and Carboniferous basalt (0.70562–0.70995), suggesting mixed source of calcite from the ore fluids and Devonian wallrocks. The ore-related calcite has δ13CPDB (−4.53 to − 2.33 ‰) and δ18OSMOW (+14.98 to + 16.30 ‰) values that fall between the granite and marine carbonate isotopic fields. This suggests that the ore-forming fluid may be related to the low-temperature alteration of granites and marine carbonate dissolution. Simulated precipitation temperature calculation for the ore-related calcite yielded 200–150 °C, and the calcite C-O isotopes suggest that fluid mixing, fluid-rock interactions, and CO2 degassing may have precipitated the stibnite in the fracture zones under low-temperature conditions. Our new geochemical results and published data suggest that the Yangla polymetallic mineralization was multiphase, comprising the Indosinian Cu-Pb-Zn (∼230 Ma), Yanshanian Sb (∼155 Ma), and Himalayan W-Sb (∼30 Ma) metallogenic events.