Rational design and synthesis of highly efficient nanocatalysts towards electrochemical ethanol oxidation reaction (EOR) are of great importance for practical applications in direct ethanol fuel cells. Nanoengineering the nanostructures and compositions of EOR electrocatalysts has been of significnat interest because these paratmeters can enhance electrocatalytic kinetics and performance in the EOR. This article reports a synergistic EOR catalyst with remarkably enhanced electrochemical performance based on 3-nm-thick bimetallic PdAg single-crystalline nanowires. Kinetically stable yet thermodynamically unfavorable ultrathin PdAg single-crystalline nanowires (sNWs) are epitaxially grown in situ along nanoconfined hexagonal mesophases directly self-assembled by amphiphilic surfactants of dioctadecyldimethylammonium chloride under optimal synthetic condtions in aqueous solution. Due to the ultrathin and ultralong nanostructure, single-crystalline feature with a high density of low-coordinate atomic steps, high Pd utilization efficiency, and incorporation of more oxophilic Ag with Pd, PdAg sNWs show enhanced mass activity of 2.84 A mg(Pd)(-1) and stability (retained 43% after 2500 cycles) in the EOR. The kinetic studies reveal that significant enhancement in EOR performance can be ascribed to the synergic electronic and bifunctional effects of ultrathin PdAg sNWs.