Methanol may play a major role in a hydrogen economy by serving as one of the highest energy density compounds available; however, the precise reaction pathways for methanol oxidation catalysts have yet to be fully elucidated. Herein, a combination of packed-bed reactor studies and high-vacuum surface science techniques was used to elucidate the reaction mechanism of methanol oxidation over a Pt/TiO2 catalyst. The reactor studies highlight that methyl formate is produced under mild reaction conditions, and full combustion to CO2 is achieved at elevated catalyst temperatures. The surface science experiments show that the production of CO2 proceeds through a surface-bound formate intermediate via multiple proton-coupled electron-transfer steps. Importantly, we also find that the water produced upon initial methanol adsorption plays a key role in unlocking the oxidative chemistry of this Pt-based material. These results provide valuable insight into potential modifications that could preferentially direct catalyst activity toward partial or full oxidation, thereby unlocking methods for producing valuable commodity chemicals.