The current work mainly focuses on exploring the impact of B-site partial substitution on the physico-chemical property and the catalytic performance of LaM0.25Co0.75O3 (M = Cu, Mn, Fe) perovskites for the catalytic reduction of NO by CO. Measurements are applied to characterize the gained catalysts, including XRD, N-2-physisorption (BET), H-2-TPR, O-2-TPD, ICP-AES, XPS and in situ DRIFTS. The results are listed below: (1) with partial substitution of foreign cations, the perovskite structure of LaCoO3 is maintained effectively with improved catalytic performance; (2) the reduction property and content of oxygen defect sites of partial substituted catalysts are the key factors for the improved catalytic performance; (3) the partial substitution of copper obviously reduces the impact of the restriction for CO adsorption by NO preferential adsorption on LaCoO3 catalyst; (4) the partial substitution of copper distinctly promotes the reducing capacity and adsorption of gaseous 02 for LaCoO3. Besides, taking LaCu0.25Co0.75O3 catalyst as an example, a reliable catalytic model is tentatively put forward to thoroughly exploring the reaction process in NO + CO reaction.