Photocatalytic CO reduction has been considered as an efficient way for the carbon nuetrality. In this work, a series of (Cu, Mn) co-incorporated metal-orgnaic frameworks (MOFs) (NH-MIL-125(Ti) (NML)) with different Cu/Ti and Mn/Ti molar ratios are systematically investigated to improve the efficiency for photocatalytic CO reduction. The optimized sample (1 M−5C−−NML) shows a highest yield of HCOOH (116.74 μmol.gh) (3.71 times higher than that of NML), and a superior apparent quantum efficiency (AQE) (6.74 % at 405 nm). The improved performance is attributed to the formed oxygen vacancy and intermediate energy level as introduced by the co-incorporation, which facilitate the charge separation and enhance the visible-light-harvesting of NML. It shows that the density of oxygen vacancies increases with the increasing amount of Cu, resulting in enhanced charge separation. However, the increasing amount of Mn leads to the short-range Mn-Mn interaction, the concentration quenching effect as well as the inhibited photocatalytic performance. This work shows that the co-incorporated MOFs can be used as an advanced photocatalyst.