Restrained by the uncontrollable cleavage process of chemical bonds in methane molecules and corresponding formed intermediates, the target product in the reaction of methane selective oxidation to methanol would suffer from an inevitable overoxidation process, which is considered to be one of the most challenging issues in the field of catalysis. Herein, we report a conceptually different method for modulating the conversion pathway of methane through the selective cleavage of chemical bonds in the key intermediates to suppress the generation of peroxidation products. Taking metal oxides, typical semiconductors in the field of methane oxidation as model catalysts, we confirm that the cleavage of different chemical bonds in CH 3 O* intermediates could greatly affect the conversion pathway of methane, which has a vital role in product selectivity. Specifically, it is revealed that the formation of peroxidation products could be significantly prevented by the selective cleavage of C−O bonds in CH 3 O* intermediates instead of metal−O bonds, which is proved by the combination of density functional theory calculations and in situ infrared spectroscopy based on isotope labeling. By manipulating the lattice oxygen mobility of metal oxides, the electrons transferring from the surface to the CH 3 O* intermediates could directionally inject into the antibonding orbitals of the C−O bond, resulting in its selective cleavage. As a result, the gallium oxide with low lattice oxygen mobility shows a 3.8% conversion rate for methane with a high methanol generation rate (∼325.4 μmol g −1 h −1 ) and selectivity (∼87.0%) under room temperature and atmospheric pressure in the absence of extra oxidants, which is superior among the reported studies (reaction pressure: <20 bar).