The relation between a catalytic center and the surrounding carbon–oxygen groups influences the catalytic activity in various reactions. However, the impact of this relation on catalysis is usually discussed separately. For the first time, we proved that carbon–oxygen groups increased the reducibility of Fe–C bonds toward NO reduction. Experimentally, we compared the reductive activities of materials with either one or both factors, i.e., carbon–oxygen groups and Fe–C bonds. As a result, graphene oxide-supported Fe (with both factors) showed the best activity, duration of activity, and selectivity. This material reduced 100% of NO to N2 at 300 °C. Moreover, theoretical calculations revealed that the adsorption energy of graphene for NO increased from −13.51 (physical adsorption) to −327.88 kJ/mol (chemical adsorption) after modification with Fe–C. When the graphene-supported Fe was further modified with carboxylic acid groups, the ability to transfer charge increased dramatically from 0.109 to 0.180 |e–|. Therefore, the carbon–oxygen groups increased the reducibility of Fe–C. The main results will contribute to the understanding of NO reduction and the design of effective catalysts.