The chemical weathering of rocks with sulfuric acid is usually not considered in reconstructions of the past evolution of the carbon cycle, although this reaction delivers cations and alkalinity to the ocean without involvement of atmospheric CO2. The contribution of sulfuric acid as a weathering agent is still poorly quantified; the identification of riverine sulfate sources is difficult. The use of δ34S and δ18O of dissolved sulfate allows us to demonstrate that most of the sulfate in surface waters of the Mackenzie River system, Canada, derives from pyrite oxidation (85% ± 5%) and not from sedimentary sulfate. The calculated flux of pyrite-derived sulfate is 0.13 × 1012 mol/yr, corresponding to 20%–27% of the estimated global budget. This result suggests that the modern global ocean delivery of sulfide-derived sulfate, and thus chemical weathering with sulfuric acid, may be significantly underestimated. A strong correlation between sulfide oxidation rates and mechanical erosion rates suggests that the exposure of fresh mineral surfaces is the rate-limiting factor of sulfide oxidation in the subbasins investigated. The chemical weathering budget of the Mackenzie River shows that more than half of the dissolved inorganic carbon discharged to the ocean is ancient sedimentary carbon from carbonate (62%) and not atmospheric carbon (38%). The subsequent carbonate precipitation in the ocean will thus release more CO2 in the atmosphere-ocean system than that consumed by continental weathering, typically on glacial-interglacial time scales.