The Farallón Negro deposit is located in the Farallón Negro Volcanic Complex (FNVC; ∼9.40 to 4.88 Ma) in NW Argentina and includes intermediate-sulfidation, epithermal Au-Ag mineralization in the Alto de la Blenda deposit. Detailed mineralogical and geochemical investigations of the Esperanza-Esperanza Sureste, Cecilia veins, both hosted in the Alto de la Blenda monzonite, and the Laboreo vein, hosted in the volcaniclastic Morada Central andesitic breccia, reveal four hypogene vein stages. Each of these four stages are comprised of a texturally early quartz, followed by a sulfide-sulfosalt and a late Mn-carbonate sub-stage. Stage 1 is characterized by a quartz, base metal and Mn-carbonate sub-stage showing high δ18OVSMOW (δ18OQuartz = 13.7 ± 0.4‰ and δ18OMn-Calcite = 11.6 ± 0.2‰) and low δ13CVPDB values (δ13CMn-Calcite = –4.7 ± 0.2‰). Stage 2 includes most gold and silver minerals in a tennantite-tetrahedrite-sphalerite-pyrite-galena±electrum sub-stage. Fluid inclusions trapped in vein-anhydrite, only associated with stage 2, record the highest temperatures (TEntrapment = 327–335°C) and highest salinity (3.8NaCleq.wt.%) when compared to all other stages. Stage 2 quartz (δ18OQuartz = 9.9 to 11.9‰) and carbonate display lower δ18OVSMOW (δ18OMn-Calcite = 7.9 to 10.3‰), as well as lower δ13CVPDB values (δ13CMn-Calcite = -5.2 to 4.7‰) than all other stages. Stages 3 and 4 consist of barren quartz and carbonate sub-stages that show lower temperatures (TEntrapment = 187–262°C) and higher δ18OVSMOW (δ18OQuartz = 13.4 to 13.9‰ and δ18OMn-Calcite = 10.7 to 11.8‰) and δ13CVPDB values (δ13CMn-Calcite = –3.5 to −3.9‰) when compared to earlier stages.Petrographic, sulfide mineral chemistry, microthermometric, and stable isotope data combined with distinct alteration mineral assemblages allow the reconstruction of a model for the Alto de la Blenda deposit. During the hypogene hydrothermal fluid flow stage, around 7.16 Ma, at ∼2.2 km depth (PHYDROSTATIC = 220 bars), the high temperature alteration mineralogy, low fluid salinities and 18O and 13C isotope compositions indicate cooling of ascending magmatic-hydrothermal fluids. These fluids were derived from a contracted magmatic vapor phase that exchanged with unexposed sedimentary rocks of the Sierras Pampeanas. Hypogene quartz-R3 illite/smectite-chlorite-calcite-pyrite alteration in the andesitic-breccia and quartz-illite-R3 illite/smectite-chlorite-calcite-pyrite alteration in the monzonite are temporally and spatially to the hydrothermal vein minerals deposited between 187 and 335°C. During the post-hydrothermal supergene weathering event, around 2.70 Ma, sulfuric acids generated by meteoric fluids and supergene oxidation of hypogene sulfides, particularly pyrite, descended along normal fault zones and related vein and fracture networks to at least 450 m depth below the surface level, forming the supergene alteration assemblage of dioctahedral smectite-kaolinite-Mn-/Fe-oxides/-hydroxides-gypsum±interstratified chlorite/smectite±interstratified R1 illite/smectite in both wall rock types at temperatures <50°C.The dominant hypogene alteration assemblage, present in the monzonite and volcaniclastic andesitic breccia, may be indicative of deeper-seated, transitional magmatic-hydrothermal systems (>1 km depth), generally controlled by fluid cooling, as is the case at Farallón Negro. Pervasive supergene alteration can conceal these systems but the identified supergene alteration assemblage of dioctahedral smectite-kaolinite-interstratified chlorite/smectite-interstratified R1 illite/smectite that replaces the hypogene alteration assemblage along the permeable fault, vein and fracture zone network may present a useful vectoring tool towards concealed, deeper-seated, epithermal Au-Ag mineralization in arid climates.