Metal-based catalysis has significantly contributed to the chemical community especially in environmental science. However, the knowledge of cobalt-based perovskite for aqueous phase oxidation still remains equivocal and insufficient. In this study, we discovered that Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) perovskite was exclusively effective for peroxymonosulfate (PMS) activation to produce free radicals, whereas the BSCF was inert to activate peroxydisulfate (PDS) and hydrogen peroxide. The BSCF/PMS exhibited superior performance to the benchmark Co3O4 nanocrystals and other classical PMS activators such as α-MnO2 and spinel CoFe2O4, meanwhile achieving an impressive stability with manipulated cobalt leaching in neutral and basic environment. In situ electron paramagnetic resonance (EPR) revealed the evolution of massive sulfate radicals (SO4[rad]−) and hydroxyl radicals ([rad]OH) during the oxidation. A comprehensively comparative study of BSCF and Co3O4 nanocrystals was performed, including electrochemical impedance spectroscopy (EIS) and cyclic voltammograms (CV) in PMS solution as well as hydrogen temperature-programmed reduction (H2-TPR) and oxygen temperature-programmed desorption (O2-TPD) tests. The results unveil that the cobalt-based perovskite, BSCF, exhibited a better electrical conductivity and redox potential than the spinel cobalt oxide to interact with PMS. More importantly, the oxygen vacancies and less-electronegativity A-site metals may secure cobalt sites with a lower valence state for donating electrons to PMS simultaneously for radical generation. This study advances the mechanism of cobalt-based heterogeneous catalysis in environmental remediation.