Cu-based catalysts featured with high activity at low temperatures and suppressed CO generation are expected to attract significant attention in the methanol steam reforming (MSR) reaction for on-board hydrogen production for proton exchange membrane fuel cells. Herein, we demonstrate that Ag incorporation into a CuO/ZnO/Al2O3 catalyst leads to enhanced hydrogen production activity and suppressed CO selectivity in MSR reactions at low temperatures (200–220 °C). The characterization results revealed that incorporation of a small amount of Ag in the catalyst not only improves the dispersion of the polymetallic components and diversifies the Cu species, but also lowers Cu reduction temperature and brings more oxygen vacancies, thereby leading to improved catalytic performance. The preparation conditions, structure-activity relationship, and stability of the Ag-promoted catalyst were investigated in detail based on time-on-steam tests and characterizations. This finding paves a new possible way for the optimization of the Cu-based catalysts for MSR.