Defect engineering in catalytic materials is a versatile strategy to fine-tune their performance towards oxidation reactions, and break the related bottlenecks. Herein, a series of La1−xMnO3 perovskite-based materials was designedly synthesized to investigate the effect of cation defects on their physico-chemical properties. Based on extensive characterizations and density function theory (DFT) calculations, it is demonstrated that La-deficiency could orderly induce oxygen vacancies and electronic structure regulation on perovskite, which prominently promotes the catalytic activity towards formaldehyde oxidation. The leading material (La0.6MnO3) could retain high activity for 63 h, either under dry or humid air. In brief, this work unveils the feasibility of modulating the surface reactivity by modifying the electronic structure properties of lanthanum manganite perovskites following simple adjustment of the A-site cationic vacancies, and also highlights A-site deficient perovskite as a potentially efficient catalyst for environmental remediation.