Oxidative coupling of methane reaction pathways on MgO and lithium-modified MgO were theoretically studied using the semiempirical MNDO-PM3 molecular orbital method. The surface of the MgO catalyst was modeled by a Mg9O9 molecular cluster containing structural defects such as edges and corners. Lithium-promoted magnesia was simulated by isomorphic substitution of Mg2+ by Li+; the excess negative charge of the cluster was compensated by a proton connected to a neighboring O2- site. Heterolytic adsorption of methane was found to be directly related to the coordination number of both the lattice oxygen and the metal sites. Energetically the most favorable site pair was Mg-3c-O-3c with a neighboring Li-4c site present. Various sequential oxygen and methane adsorption pathways were explored resulting in CH3OH formation with lower energy barriers for the Li-modified MgO cluster as compared to unmodified MgO.