The influence of radiation-induced (1 MeV energy H+ to ∼0.1 displacements per atom (dpa) at 450 °C), nonequilibrium point defect populations on mass transport is studied with an integrated campaign of experimental and theoretical methods. Using epitaxial thin films of hematite (α-Fe2O3) with embedded 18O tracer layers and nanoscale atom probe tomography measurements, it is shown that anion self-diffusion is enhanced by at least 2 orders of magnitude under irradiation compared to thermal diffusion alone. Complementary scanning transmission electron microscopy of vacuum-annealed and irradiated specimens reveals associated microstructural changes near the surface of the oxide films, including local phase transformation to Fe3O4 and the development of nanoscale voids from vacancy coalescence. Point defect formation and migration energies were computed from density functional theory and applied within the context of the chemical rate theory to analyze contributions from both interstitial and vacancy mechanisms to self-diffusion in thermal and irradiation conditions. Comparisons are made between calculated, literature, and newly measured self-diffusion values, revealing good agreement on the magnitude of radiation-enhanced anion diffusion. Further, the model suggests a transition from vacancy to interstitialcy mechanisms at low temperatures and high oxygen activity, providing an explanation for the varied activation energies reported from prior studies. © 2021 American Chemical Society.