The adsorption of CO on Cu13 and defective graphene-supported Cu13 clusters is investigated using ab initio molecular dynamics methods. The results show that the CO adsorption energies on the defective graphene-supported Cu13 cluster are substantially enhanced compared to those on the Cu13 cluster. Furthermore, the average adsorption energy on the defective graphene-supported Cu13 cluster is significantly increased by 155% compared with the experimental one on pristine Cu surfaces, indicating that the defective graphene-supported Cu13 cluster can be an excellent catalyst for CO adsorption. The enhancement of the adsorption energies can be qualitatively explained in terms of the crystal orbital Hamilton population, that is, as the bond interaction increases, the adsorption energy increases. We propose an induction energy model to calculate the amount of the adsorption energy enhancement. The predicted adsorption energies on the defective graphene-supported Cu13 clusters are in quantitative agreement with those obtained from ab initio molecular dynamics simulations. The current study provides insights into designing highly active catalysts for CO adsorption.