Mineral weathering plays a primary role in the geologic carbon cycle. Silicate weathering by carbonic acid consumes CO2 and stabilizes Earth’s climate system. However, when sulfuric acid drives weathering, CO2 can be released to the atmosphere. Recent work has established that sulfuric acid weathering resulting from sulfide mineral oxidation is globally significant and particularly important in rapidly eroding environments. In contrast, if SO42– produced by sulfide oxidation is reduced during continental transit, then CO2 release may be negated. Yet, little is known about how much SO42– reduction takes place in terrestrial environments. We report oxygen and sulfur stable isotope ratios of SO42– in river waters and mass budget calculations, which together suggest that SO42– released from pyrite oxidation in the Peruvian Andes mountains is conservatively exported across ~300 km of the Amazon floodplain. In this system, floodplain SO42– reduction does not counteract the large SO42– flux from Andean pyrite weathering or measurably affect the stable isotope composition of riverine SO42–. These findings support the hypothesis that uplift and erosion of sedimentary rocks drive release of CO2 from the rock reservoir to the atmosphere.