Simultaneously improving both NO_x conversion and N₂ selectivity in the selective catalytic reduction of NO by CO (CO-SCR) under O₂-containing conditions is highly challenging because of the competitive reactions of NO_x and CO with O₂. Here, we demonstrate that the interfacial oxygen vacancies (IOVs) generated at the Co₃O₄-CeO₂ heterointerfaces by ball-milling-induced strain can remarkably boost both NO_x conversion and N₂ selectivity in the temperature range of 100–400 °C. The Co₃O₄-CeO₂-IOV catalyst achieved approximately 100% NO_x conversion and 100% N₂ selectivity (200–350 °C, 1–5 vol% O₂, and 20,000 h⁻¹); even under 10 vol% O₂, it still showed good catalytic performance. The spectroscopy analysis and theoretical calculations reveal that compared with O₂ activation, IOVs are more favorable for the rate-limiting step of NO adsorption and dissociation. This work provides an effective strategy to create IOVs within metal oxide composite catalysts using ball-milling-induced interfacial strain for improving CO-SCR performance.