Abstract Enhancing the catalytic activity of Pt‐based alloy by a rational structural design is the key to addressing the sluggish kinetics of direct alcohol fuel cells. Herein, a facile one‐pot method is reported to synthesize PtCuRu nanoflowers (NFs). The synergetic effect among Pt, Cu, and Ru can lower the d‐band center of Pt, regulate the morphology, generate Ru‐rich edge, and allow the exposure of more high index facets. The optimized Pt 0.68 Cu 0.18 Ru 0.14 NFs exhibit outstanding electrocatalytic performances and excellent anti‐poisoning abilities. The specific activities for the methanol oxidation reaction (MOR) (7.65 mA cm −2 ) and ethanol oxidation reaction (EOR) (7.90 mA cm −2 ) are 6.0 and 7.1 times higher than commercial Pt/C, respectively. The CO stripping experiment and the chronoamperometric (5000 s) demonstrate the superior anti‐poisoning property and durability performance. Density functional theory calculations confirm that high metallization degree leads to the decrease of d‐band center, the promotion of oxidation of CO, and improvement of the inherent activity and anti‐poisoning ability. A Ru‐rich edge exposes abundant high index facets to accelerate the reaction kinetics of rate‐determining steps by decreasing the energy barrier for forming *HCOOH (MOR) and CC bond breaking (EOR).