The occurrence of red shales in Precambrian sedimentary rocks has been used to infer the presence of free O2 in the atmosphere. Red shale samples from the ~2.2 Ga Gamagara/Mapedi Formation of the Postmasburg Group, South Africa were analyzed for mineralogy, geochemistry, and stable isotope composition (Fe and organic C) to constrain the timing and mechanism of red shale formation. These data suggest that the red shales were detrital accumulations of lateritic soils that were produced from moderate to intense chemical weathering of intermediate to felsic source rocks. Such weathering occurred under stable climatic conditions in low-latitude (sub)tropical regions. The data also suggest that the red shales were potentially influenced by hydrothermal activity. Hematite, a pigmenting agent of the red shales, was probably formed during the lateritic weathering of the source rocks ~2.2 Ga ago, rather than by the modern oxidation/weathering of pre-existing Fe2+-bearing minerals in the shales. Dissolution, remobilization, and reprecipitation of Fe and U during the diagenetic stage of shales are suggested from variations in the Fe3+/Ti, Fe2+/Ti, Fe isotope compositions, and U/Th ratios. Leaching of Fe2+-bearing silicate and/or reductive dissolution of Fe3+-oxide minerals, probably by organic acids, resulted in the discoloration of several red shales (to pale-green/white) during red shale diagenesis. Oxidation of Fe2+ on the seafloor that was supplied by hydrothermal discharge and migration (upward diffusion) of leached Fe2+ in sediments was additional source of Fe3+ for red shale formation. Geochemical evidence thus supports the existence of an oxygenated atmosphere and shallow ocean system at least ~2.2 Ga ago.