Previous experimental studies have shown that the activation energy for methanol oxidation by naturally occurring Ca2+-containing methanol dehydrogenase (MDH) enzyme is double the methanol activation energy by Ba2+-MDH. However, neither the reason for this difference nor the specific transition states and intermediates involved during the methanol oxidation by Ba2+-MDH have been clearly stated. Hence, an MDH active site model based on the well-documented X-ray crystallographic Structure of Ca2+-MDH is selected, where the Ca2+ is replaced by a Ba2+ ion at the active site center, and the addition-elimination (A-E) and hydride-transfer (H-T) methanol oxidation mechanisms, already proposed in the literature for Ca2+-MDH, are tested for Ba2+-MDH at the BLYP/DNP theory level. Changes in the geometries and energy barriers for all the steps are identified, and qualitatively, similar (when compared to Ca2+-MDH) intermediates and transition states associated with each step of the mechanisms are found in the case of Ba2+-MDH. For both the A-E and H-T mechanisms, almost all the free-energy barriers associated with all of the steps are reduced in the presence of Ba2+-MDH, and they are kinetically feasible. The free energy barriers for methanol oxidation by Ba2+- MDH, particularly for the rate-limiting steps of both mechanisms, are almost half the corresponding barriers calculated for the case of Ca2+-MDH, which is in agreement with experimental observations.