Direct ethanol fuel cells have broad application prospects, but there are still some issues such as slow oxidation kinetics and poisoning effects of intermediates in the anodic ethanol reduction reaction (EOR). Herein, a series of few‐layer Ag‐coated ordered mesoporous Pt nanocrystals (Meso‐Pt@Ag) with different Ag shell thicknesses are prepared by combining hard templating and in situ reduction methods. Benefiting from the ordered mesoporous structure, the lattice strain, and the electronic synergistic effect induced by the core–shell structure, Meso‐Pt@Ag2 nanocrystals exhibit the best EOR performance with a mass activity of 10.01 A mgPt−1, which is 8.40‐fold of commercial Pt/C and 4.45‐fold of Meso‐Pt, respectively. And, Meso‐Pt@Ag2 nanocrystals also show the favorable toxicity resistance to carbonaceous intermediates and stability for EOR. Furthermore, theoretical calculations demonstrate that the Ag‐coated Pt core has more optimized deprotonation reaction kinetics and lower CO adsorption energy, indicating its better resistance to CO toxicity for EOR.