The catalytic activity of metal oxide-supported Pt–MOx (M=Mo, W, Ce, V) catalysts was investigated for methanol reforming to hydrogen at low temperatures with varied reaction pressures in gaseous to aqueous phase regimes. The Pt–MoOx/TiO2 catalysts prepared through co-impregnation of the precursors demonstrated unprecedentedly high catalytic activities compared with the previously reported Pt-based catalysts, which showed an order of magnitude higher hydrogen production turnover rates with extremely low CO selectivities. The morphological and electrochemical characteristics of the dispersed Pt–MoOx nanoclusters were largely affected by the impregnation method and the Mo/Pt atomic ratio. The Pt–MoOx nanoclusters consisting of metallic state Pt and MoOx moieties of high site density and reducibility capable of Mo6+ to Mo5+ redox transition promoted the marked rate enhancements in methanol reforming to hydrogen at low temperatures. These highly active catalysts offer opportunities in the direct embedding of fuel processing in polymer electrolyte membrane fuel cells through the internal thermal integration of exothermic electrochemical reactions with endothermic fuel reforming for hydrogen production.