The Bétaré Oya district has a substrate composed of the Neoproterozoic metavolcanic-metasedimentary rocks of the Lom Belt in eastern Cameroon. The district is well-known for alluvial gold mining activities, however, the primary gold mineralization has received little attention. In the current study, we newly report geological, ore mineralogy, fluid inclusion microthermometric, laser Raman spectroscopy, and stable isotope data from auriferous veins of the Lom Belt to characterize the style of gold mineralization and to constrain the origin of the ore-forming fluids. The auriferous quartz veins are laminated, fractured, N- to NE-trending, and spatially associated with the Bétaré Oya Shear Zone. Fieldwork coupled with microscopic examination and the textural relationships of ore minerals revealed two stages of mineralization. The first stage is characterized by the presence of pyrite, sphalerite, galena, chalcopyrite, pyrrhotite, hematite, petzite, hessite, wolframite, electrum, and gold, while the second stage is characterized by the presence of a later deposition of galena and pyrite, as well as minor greenockite. The gangue minerals are quartz, sericite, muscovite, chlorite, calcite, ankerite, and barite, whereas the supergene assemblage (stage 3) includes goethite, hematite, covellite, and enargite. Two fluid inclusion assemblages containing three types of inclusions are identified in mineralized quartz veins. Assemblage 1 consists of gold-related types 1 and 2 with daughter minerals consisting of nahcolite, magnesite, and arsenolamprite (black native arsenic), whereas assemblage 2 consists of post-gold type 3 fluid inclusions. Type 1 has H2O-NaCl-CO2 ± N2 ± CH4 primary fluid inclusions (FI), with a TmCO2 ranging from −59.8 to −56.6 °C, salinities from 0.5 to 10.8 wt% NaCl eq., densities from 0.87 to 1.00 g.cm−3, and total homogenization temperatures between 280 and 360 °C. Type 2 contains CO2 (±H2O-NaCl) ± N2 ± CH4 FI that exhibit TmCO2 ranging between −60.0 and −56.7 °C, ThCO2 from 13 to 25 °C, and densities between 0.73 and 0.85 g.cm−3. Type 3 shows H2O-NaCl FI with salinities between 0.2 and 10.1 wt% NaCl eq., densities between 0.82 and 0.98 g.cm−3, and total homogenization temperatures from 160 to 235 °C. Measured δ18O for gold-bearing quartz (+11.5 to +16.0‰), δD from FI (−50.6 to −21.8‰), δ13C from FI (−5.8 to −5.5‰), and δ34S from galena and pyrite grains (+5.3‰ and +8.2‰, respectively) suggest a metamorphic source as most likely for the ore-forming fluids and sulfur, although a mantle CO2 contribution cannot be ruled out.The gold deposition probably took place by fluid-rock interaction and fluid unmixing at ∼310 °C and at a depth of about 6–9 km. The ore-forming fluid was a low salinity (∼6.2 wt% NaCl eq.) H2O-NaCl-CO2 ± N2 ± CH4 solution. These data revealed that the Lom Belt gold mineralization is best classified as a mesozonal orogenic gold deposit.