The response of polycrystalline SrTiO3, fabricated by the flash sintering method, to ion beam irradiation was investigated by means of transmission electron microscopy (TEM) and atomic scale modeling. The samples were implanted with 250 keV Ne ions at fluences between 1.11 × 1016 and 2.25 × 1016 ions per cm2 at room temperature and then characterized using scanning transmission electron microscopy and high voltage TEM. We observed that this material has a large number of Ruddlesden–Popper (RP) faults, related to the non-stoichiometry of the material, in a random and sometimes complicated arrangement. These faults have a significant impact on the radiation damage evolution of the material. In particular, the faults amorphize more quickly than the surrounding SrTiO3 matrix. We examined the interaction of point defects with the RP faults using atomistic modeling and determined that both the thermodynamic and kinetic properties of defects are significantly influenced by the presence of the faults, providing insight into the experimental observations. We conclude that planar defects such as RP faults can have a significant impact on the radiation damage evolution of SrTiO3 and might be one avenue for controlling radiation tolerance in complex materials.