In light of the good performance of Mo-based catalysts for sulfur-resistant CO methanation, we investigated the reaction mechanism over pure MoS2 in a previous study, in which the Mo-edge from (0 1 0) surface of MoS2 was found inactive due to the difficulty in S-vacancy creation. It was generally recognized that Co is a good additive on Mo-based catalyst for CO methanation. Thus, we focused on promoting the Mo-edge by presenting a group of cobalt substituted surface models via DFT simulation. These models were all reconstructed by performing a thermodynamic investigation on the numbers of the created S-vacancies according to the reaction condition of CO methanation from experimental data. Based on the discussion of reaction pathways over four determined surfaces, we found that a substitute ratio of 0.25 and 0.50 in ortho-position can exhibit the highest catalytic activities, but a substitute ratio of 0.50 in meta-position exhibits the optimum stability in the overall reaction.