Platinum is the most active anode and cathode catalyst in next-generation fuel cells using methanol as liquid source of hydrogen. Its catalytic activity can be significantly improved by alloying with 3d metals, although a precise tuning of its surface architecture is still required. Herein, we report the design of a highly active low temperature (below 0 • C) methanol dehydrogenation anode catalyst with reduced CO poisoning, based on ultra-low amount of precisely-defined PtxNi1-x (x = 0 to 1) bimetallic clusters (BCs) deposited on inert flat oxides by Cluster Beam Deposition (CBD). These BCs feature clear composition-dependent atomic arrangements and electronic structures stemming from their nucleation mechanism that are responsible for a volcano-type activity trend peaking at the Pt0.7Ni0.3 composition. Our calculations reveal that at this composition a cluster skin of Pt atoms with d-band centres downshifted by subsurface Ni atoms weakens the CO interaction that in turn triggers a significant increase in the methanol dehydrogenation activity.