The elimination of S-containing compounds in heavy oil is of significant importance to viscosity reduction and oil quality elevation in order to enhance oil recovery. In this study, the decomposition behavior of S-containing compounds in heavy oil was elucidated from a theoretical perspective in conjunction with simulative experiments. CH3SCH3 was employed as a model molecule on behalf of straight-chain saturated sulfides in heavy oil. The common cost-friendly inverse spinel Fe3O4 was selected as the catalyst. Our theoretical calculations revealed that the most feasible reaction pathway of entire CH3SCH3 decomposition occurred in two steps with the assistance of weakly adsorbed H2O molecules, generating two CH3OH molecules and one H2S molecule, of which the first step was the rate-determining step. These calculated results were confirmed with experimental results, which contributed to a clear and reliable catalytic desulfurization mechanism for S-containing compounds in heavy oil during aquathermolysis.