Exploring highly efficient and robust non-noble metal catalysts for VOC abatement is crucial but challenging. Mn-based perovskites are a class of redox catalysts with good thermal stability, but their activity in the catalytic combustion of light alkanes is insufficient. In this work, we modulated the Mn–O bond strength in a Mn-based perovskite via defect engineering, over which the catalytic activity of propane combustion was significantly enhanced. It demonstrates that the oxygen vacancy concentration and the Mn–O bond strength can be efficiently modulated by finely tuning the Ni content in SmNixMn1–xO3 perovskite catalysts (SNxM1–x), which in turn can enhance the redox ability and generate more active oxygen species. The SN0.10M0.90 catalyst with the lowest Mn–O bond strength exhibits the lowest apparent activation energy, over which the propane conversion rate increases by 3.6 times compared to that on the SmMnO3 perovskite catalyst (SM). In addition, a SN0.10M0.90/cordierite monolithic catalyst can also exhibit a remarkable catalytic performance and deliver excellent long-term durability (1000 h), indicating broad prospects in industrial applications. Moreover, the promotional effect of Ni substitution was further unveiled by density functional theory (DFT) calculations. This work brings a favorable guidance for the exploration of highly efficient perovskite catalysts for light alkane elimination.