Developing an efficient Pt-based electrocatalyst with well-defined structures for the methanol oxidation reaction (MOR) is critical, however, still remains a challenge. Here, a one-pot approach is reported for the synthesis of Pd3Pb/Pt n Pb nanocubes with tunable Pt composition varying from 3.50 to 2.37 and 2.07, serving as electrocatalysts toward MOR. Their MOR activities increase in a sequence of Pd3Pb/Pt3.50Pb << Pd3Pb/Pt2.07Pb < Pd3Pb/Pt2.37Pb, which are substantially higher than that of commercial Pt/C. Specifically, Pd3Pb/Pt2.37Pb electrocatalysts achieve the highest specific (13.68 mA cm-2) and mass (8.40 A mgPt -1) activities, which are ≈8.8 and 6.8 times higher than those of commercial Pt/C, respectively. Structure characterizations show that Pd3Pb/Pt2.37Pb and Pd3Pb/Pt2.07Pb are dominated by hexagonal-structured PtPb intermetallic phase on the surface, while the surface of Pd3Pb/Pt3.50Pb is mainly composed of face-centered cubic (fcc)-structured Pt x Pb phase. As such, hexagonal-structured PtPb phase is much more active than the fcc-structured Pt x Pb one toward MOR. This demonstration is supported by density functional theory calculations, where the hexagonal-structured PtPb phase shows the lowest adsorption energy of CO. The decrease in CO adsorption energy and structural stability also endows Pd3Pb/Pt n Pb electrocatalysts with superior durability relative to commercial Pt/C.