Across a 1.2-mm-wide domain, a calcite crystal from a granulite-facies marble from East Antarctica exhibits microscale oxygen isotope heterogeneity that has been enhanced by channelized fluid flow. The oxygen isotope compositions range over 21‰—a gigantic zonation. Calcite along a boundary with phlogopite has an average δ18O value of −5‰; along a profile that extends about 700 µm into the grain, the oxygen isotope composition remains constant, indicating equilibrium with source fluids of meteoric origin. Analyses of a transect away from the phlogopite show the δ18O values rising to +16‰. The corresponding carbon isotope variation is only about 0.6‰. Isotope heterogeneity is observed mainly in a phlogopite-rich zone where the δ18O values are lower (13‰ ± 5‰) than those away from the zone (17‰ ± 1‰). We inferred that preferential microfracturing and hydrothermal fluid flow were the causes of the 18O distribution. The constant values of both δ18O and δ13C for the distance of 700 µm from the grain boundary suggest a solution-reprecipitation mechanism, whereas the smoothly increasing δ18O and decreasing δ13C values farther along the profile indicate a diffusion-controlled isotope exchange between the reprecipitated calcite and the original grain (core). Our results provide important evidence for the mechanism of isotope exchange between fluids and minerals and have major implications for microfracture-controlled fluid-flow processes in the Earth's crust.