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Oxidation of the sub-arc mantle driven by slab-derived fluids has been hypothesized to contribute to the formation of gold deposits in magmatic arc environments that host the majority of metal resources on Earth. However, the mechanism by which the infiltration of slab-derived fluids into the mantle wedge changes its oxidation state and affects Au enrichment remains poorly understood. Here, we present the results of a numerical model that demonstrates that slab-derived fluids introduce large amounts of sulfate (S6+) into the overlying mantle wedge that increase its oxygen fugacity by up to 3 to 4 log units relative to the pristine mantle. Our model predicts that as much as 1 wt.% of the total dissolved sulfur in slab-derived fluids reacting with mantle rocks is present as the trisulfur radical ion, S3–. This sulfur ligand stabilizes the aqueous Au(HS)S3– complex, which can transport Au concentrations of several grams per cubic meter of fluid. Such concentrations are more than three orders of magnitude higher than the average abundance of Au in the mantle. Our data thus demonstrate that an aqueous fluid phase can extract 10 to 100 times more Au than in a fluid-absent rock-melt system during mantle partial melting at redox conditions close to the sulfide-sulfate boundary. We conclude that oxidation by slab-derived fluids is the primary cause of Au mobility and enrichment in the mantle wedge and that aqueous fluid-assisted mantle melting is a prerequisite for formation of Au-rich magmatic hydrothermal and orogenic gold systems in subduction zone settings.