We investigated topochemical anion exchange reactions for a ScIII-substituted SrTiIVO3 perovskite, Sr(Ti1–yScy)O3–y/2□y/2 (y ≤ 0.1), using CaH2. It was found that the initial introduction of a small amount of anion vacancies (y/2) is crucial to enhance the anion (H–/O2–) exchangeability. For example, hydride reduction of Sr(Ti0.95Sc0.05)O2.975 yielded the oxyhydride SrTi0.95Sc0.05O2.56H0.41 in which the hydride concentration is increased by 33% with respect to pristine SrTiO3 (leading to SrTiO2.76H0.24). This observation highlights the importance of anion vacancies to improve anion (H–/O2–) diffusion, which is a well-known strategy for improving oxide anion conductivity, and suggests that such a vacancy-assisted reaction could be applied to other anion exchange reactions (e.g., F–/O2– and N3–/O2–) to extend the solubility range.