Multiple sulfur isotopes in sulfides were measured by in situ Secondary Ion Mass Spectrometry in order to constrain sulfur sources and pathways, as well as explore atmosphere–ore genesis implications on the metallogeny of the Neoarchean and Paleoproterozoic Cu-Au systems of the Carajás Domain, southeast Amazonian Craton, Brazil. All of the investigated Neoarchean (2.70–2.57 Ga; i.e., Salobo, Igarapé Bahia, Castanha and Sequeirinho) and Paleoproterozoic IOCG (ca 1.88 Ga; i.e., Alvo 118 and Sossego) deposits show Δ33S < 0‰ (-0.17‰ to + 0.02‰). The Paleoproterozoic Cu-Au(W-Sn-Bi) Breves deposit reveals Δ33S > 0‰ (+0.08‰ to + 0.27‰), implying that sulfur underwent mass-independent fractionation (MIF). In addition, three distinct δ34S ranges are defined: −3.07‰ to + 3.01‰ and + 2.17‰ to + 4.68‰ for the Neoarchean and Paleoproterozoic IOCG deposits, respectively, and −0.46‰ to + 3.81‰ for the Paleoproterozoic Breves deposit. In the Neoarchean IOCG deposits, sulfur is most likely of mantle/magmatic origin. However, a subtle but detectable MIF-S signature reflects the inheritance of a minor sulfur component transported to the atmosphere, experienced photolytic reactions and returned to the hydrosphere. The interaction between highly saline, hot, and deep-seated metalliferous fluids with the host rocks, including sulfate-bearing volcanic rocks that underwent seafloor alteration, may account for the small negative Δ33S values in the IOCG deposits. The similarity between the negative Δ33S signatures of the Neoarchean and the Paleoproterozoic IOCG deposits (i.e., Sossego and Alvo 118) suggest that the MIF signatures recorded by the latter most likely reflect inheritance of Neoarchean sulfur with MIF signatures acquired by large scale fluid-rock interaction triggered by the ca 1.88 Ga A-type granitic magmatism. The positive Δ33S values of sulfides from the Paleoproterozoic Breves deposit, in contrast, were probably generated by reduced sulfur species sourced from crustal sources (e.g., Archean pyrite-bearing sedimentary units) in addition to magmatic sulfur related to ca. 1.88 Ga A-type granite emplacement.