Ulug-Sair Au-Bi-Te-Se mineralization is one prospect for native Au in the Western Tuva, and its origin remains debated. Mineralization consists of gold–sulfide–quartz veins in the host sedimentary rocks (conglomerates, siltstones, shales), quartz–tourmaline, and quartz–carbonate–sericite–altered rocks. To determine its origin, we examined the mineralogical–geochemical features, formation conditions, and fluid sources of the Ulug-Sair ore. A mineralogical–geochemical investigation outlines two substages with Au: an early gold–sulfide–quartz with pyrite, chalcopyrite, galena, gold, and electrum; and a late gold–telluride–sulfide–quartz, characterized by the presence of Bi-bearing minerals (AgBiTe, Bi2Te2Se, Cu3BiS3, Bi), tellurides (Au and Ag), Se-tellurides (Ag and Bi), and selenides (Au, Ag, and Hg). The paragenesis of Au–Ag tellurides, and fluid inclusion study data (microthermometry, Raman spectroscopy, LA-ICP-MS, and crush leach analysis (gas and ion chromatography, ICP-MS) in quartz showed that quartz–tourmaline-altered rocks were formed by an aqueous Mg–Na–K-chloride fluid with a salinity of 8–10 wt % NaCl eq. at 325–370 °C, whereas the host quartz–carbonate–sericite-altered rocks were formed from CO2–H2O fluid containing CH4 and N2, with a salinity of 0.18–6.1 wt % NaCl eq. at 200–400 °C. Gold-bearing mineral assemblages were formed at P ~ 0.75–1.0 kbar (~2.3–3 km) due to CO2–H2O chloride (Na–K ± Fe, Mg) fluid with CH4, Na2SO4, and Na2B2O5, and salinities 1.7–12.5 wt % NaCl eq. at temperatures decreasing from 360 up to 115 °C (gold–sulfide–quartz veins—360–130 °C, and gold–telluride–sulfide–quartz veins—330–115 °C), and variable fO2, fS2, fSe2, and fTe2. Results of the investigation of the isotope composition of S in pyrites indicates the magmatic origin of the fluid (δ18SH2S fluid from −0.4 to +2.5‰). The stable O isotope data in quartz indicates that, at an early substage, the formation of ore involved a fluid of magmatic and metamorphic origin (from +8.2 to +11.6‰), and, in the later substage, multiple sources of hydrothermal fluids (from +3.1 to +10.4‰), including magmatic-derived, metamorphic-derived, and meteoric waters. These data, in conjunction with structurally controlled mineralization, point towards similarities of the Ulug-Sair ore system with orogenic gold deposits.