We investigated topochemical anion exchange reactions for a Sc-III-substituted (SrTiO3)-O-IV perovskite, Sr(Ti1-yScy)O3-y/2 square(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)O-2.975 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.