The hydrogenation of CO to high-value-added liquid fuels is crucial for greenhouse gas emission reduction and optimal utilization of carbon resources. Developing supported heterogeneous catalysts is a key strategy in this context, as they offer well-defined active sites for in-depth mechanistic studies and improved catalyst design. Here, we conducted extensive first-principles calculations to systematically explore the reaction mechanisms for CO hydrogenation on a heterogeneous bimetal NiAl-deposited metal-organic framework (MOF) NU-1000 and its catalytic performance as atomically dispersed catalysts for CO hydrogenation to formic acid (HCOOH), formaldehyde (HCO), and methanol (CHOH). The present results reveal that the presence of the NiAl-oxo cluster deposited on NU-1000 efficiently activates H, and the facile heterolysis of H on Ni and adjacent O sites serves as a precursor to the hydrogenation of CO into various C1 products HCOOH, HCO, and CHOH. Generally, H activation is the rate-determining step in the entire CO hydrogenation process, the corresponding relatively low free energy barriers range from 14.5 to 15.9 kcal/mol, and the desorption of products on NiAl-deposited NU-1000 is relatively facile. Although the Al atom does not directly participate in the reaction, its presence provides exposed oxygen sites that facilitate the heterolytic cleavage of H and the hydrogenation of C1 intermediates, which plays an important role in enhancing the catalytic activity of the Ni site. The present study demonstrates that the catalytic performance of NU-1000 can be finely tuned by depositing heterometal-oxo clusters, and the porous MOF should be an attractive platform for the construction of atomically dispersed catalysts.