The Lang Vai ore district, located in the central part of the Lo Gam domain in the Northeast Vietnam, contains at least three deposits: Khoun Puc, Lang Vai, and Lung Luong. The general paragenetic sequences for these deposits may be represented by the following mineral associations (from early to late): (i) arsenopyrite, pyrite, native gold, sphalerite; (ii) Bi-rich Pb-Sb sulfosalts; (iii) Bi-poor Pb-Sb sulfosalts; (iv) Sb sulfosalts; (v) Sb-rich minerals, native antimony; and (vi) Pb-rich Sb sulfosalts (as a distal mineral association). Three major types were recognized within the primary fluid inclusions based on the phases present at room temperature, including: V-type, vapor-rich inclusions; L-type, liquid-rich inclusions; and C-type, CO2-rich inclusions. The early Au-As stage quartz crystals contain the V- and L-type fluid inclusions. The results indicate that the initial ore-forming fluid belonged to a (CO2-CH4)–H2O–NaCl system characterized by high temperatures (290–352 °C) and variable to moderate salinities (3.16–13.89 wt% NaCl), which are analogous to reduced intrusion-related ore-forming fluids that exhibit high homogenization temperatures and moderate salinities. The quartz crystals from the Bi-Pb-Sb mineral paragenesis (occurred only at the Khoun Puc deposit) contain both V- and L-type fluid inclusions and characterized by high temperatures (mainly 304–340 °C) and moderate salinities (6.28–8.22 wt% NaCl equiv.). The quartz crystals from the middle hydrothermal stage contain the V- and L-type fluid inclusions that yield moderate homogenization temperatures (240–290 °C) and variable salinities (3.3–8.2 wt% NaCl equiv.). These features indicate that the fluid evolved into an (CO2 ± CH4)–H2O–NaCl system at moderate temperatures, lower CH4 concentrations, and variable salinities, thus indicating changing physicochemical conditions. In the last Sb stage (the Lang Vai deposit) and Pb-Sb stage (the Lung Luong deposit), the ore-forming fluid belongs to CO2–H2O–NaCl system, which is characterized by low temperature (180–240 °C), enrichment of CO2, and medium-low salinity (1.12–9.5 wt% NaCl equiv.), that corresponded to typical fluids which formed the Sb-, and distal Ag–Pb–Zn veins of the IRGS deposits in the Tintina Gold Province of Alaska USA and Yukon Canada. The fluid inclusion studies and laser Raman spectroscopy suggest that the early fluids were dominated by CH4, whereas the late fluids, by CO2. Our study suggests that the fluid boiling and accompanying decrease in the solubility of gold-bisulfide complex played an important role in gold deposition at the Khoun Puc and Lang Vai deposits. The trapping pressures estimated from the boiling fluid inclusions were 123–343 MPa during the ore-forming process. This suggests an alternating lithostatic–hydrostatic fluid system controlled by a fault-valve activity at a depth of 12.9–15.2 km. The characteristics of the S isotopes and fluid inclusions suggest that the ore-forming fluids were of magmatic origin. During mineralization process, the fluid–rock interaction between the fluids and host rocks resulted in the increase of δ34S values of the fluids as reflected in the range of sulfur isotope from the different deposits. On a plumbotectonic diagram, the sulfides show correlations between 206Pb/204Pb and both 207Pb/204Pb and 208Pb/204Pb, which suggest a two-component mixing between a high radiogenic end-member and another low radiogenic end-member. The δ13CPDB vs. δ18OSMOW study clear show that C and O in the Khoun Puc ore-forming fluids were most likely to be derived from the magma with limited contribution from the carbonate host rocks (predominantly magmatic origin of hydrothermal fluids). Wherein, the calcite separates from the Lang Vai and Lung Luong deposits have δ18OSMOW values higher than those of the Khoun Puc, suggesting that the carbonate host rocks may have provided more C and O for ore-forming fluids in these deposits. The results, combined with existing data on the regional geology, ore geology, ore geochemistry, age of mineralization, and tectonic setting, indicate that the Lang Vai ore district is an intrusion-related gold system.