Direct ethanol fuel cells (DEFCs) are promising power sources for portable electric devices owing to their high energy conversion efficiency and easy transportation of fuels. However, most electrocatalysts for DEFCs suffer from serious CO poisoning and low selectivity toward the C–C bond cleavage. Herein, we report a class of subnanometer platinum–rhodium nanowires (Pt–Rh NWs) as highly efficient electrocatalysts toward ethanol oxidation reaction (EOR). The prepared PtRh NWs have ultrathin features with an average diameter of only 1.2 nm, largely promoting Pt utilization efficiency. Combining the structural effect and synergistic effect, the optimized PtRh NWs/C shows nearly three times enhancement in activity and promoted stability for EOR compared with commercial Pt/C. Detailed mechanism studies reveal that the introduction of Rh can evidently improve the antipoisoning ability, and the PtRh NWs/C shows enhanced C–C bond cleavage ability with significant C1 pathway selectivity, all of which collectively enhance the EOR electrocatalysis.