This study develops a dual strategy of synthesis optimisation and B-site substitution to improve low-temperature CO oxidation of LaFeO3 perovskites. A modified co-precipitation method uses organic additives (F127, sucrose, citric acid) as surface area promoters and an ammonia precipitant. Four-factor three-level orthogonal experiments optimise pH, calcination temperature/time and additive type. Calcination temperature dominates performance, followed by additive species, calcination time and pH. The optimal catalyst (pH = 10, 800 °C, 3 hours, citric acid) attains 99.1% CO conversion at 300 °C via enlarged surface area and evenly distributed active phases. 20% Co substitution for Fe creates abundant lattice defects and oxygen vacancies in LaFe0.8Co0.2O3, boosting oxygen mobility and redox ability. It realises full CO conversion at 225 °C, 75 °C lower than pure LaFeO3 with stable structure. Ni/Cu/Mn doping comparisons confirm Co's optimal promotion. This work proves synergistic nanostructure modulation and defect engineering to fabricate efficient perovskites and guides low-temperature CO removal.