The Lyhamyar deposit is a large Sb deposit in the Southern Shan Plateau, Eastern Myanmar. The deposit is located in the Early Silurian Linwe Formation, occurring as syntectonic quartz-stibnite veins. The ore body forms an irregular staircase shape, probably related to steep faulting. Based on the mineral assemblages and cross-cutting relationships, the deposit shows two mineralization stages: (1) the pre-ore sedimentary and diagenetic stage, and (2) the main-ore hydrothermal ore-forming stage (including stages I, II, and III), i.e., (i) early-ore stage (stage I) Quartz-Stibnite, (ii) late-ore stage (stage II) Quartz-calcite-Stibnite ± Pyrite, and (iii) post-ore stage (stage III) carbonate. The ore-forming fluid homogenization temperatures from the study of primary fluid inclusions in quartz and calcite indicate that the ore-forming fluid was of a low temperature (143.8–260.4 °C) and moderate to high-salinity (2.9–20.9 wt. % NaCl equivalent). Hydrogen and oxygen isotopes suggest that the ore-forming fluids of the Lyhamyar deposit were derived from circulating meteoric water mixed with magmatic fluids that underwent isotopic exchange with the surrounding rocks. Sulfur in Lyhamyar was dominated by thermochemical sulfate reduction (TSR) with dominant magmatic source sulfur. The lead isotope compositions of the stibnite indicate that the lead from the ore-forming metals was from the upper crustal lead reservoir and orogenic lead reservoir. On the basis of the integrated geological setting, ore geology, fluid inclusions, (H-O-S-Pb) isotope data, and previous literature, we propose a new ore-deposit model for the Lyhamyar Sb deposit: It was involved in an early deposition of pyrite in sedimentary and diagenetic stages and later Sb mineralization by mixing of circulating meteoric water with ascending magmatic fluids during the hydrothermal mineralization stage.