Metal nanodendritic structures have attracted a lot of attention because of their high activity toward catalytic reactions. Herein, we present a facile method for the one-pot synthesis of highly branched PtCu alloy nanodendrites. The composition of the PtCu nanodendrites can be easily tuned by changing the molar ratio of the precursors. The PtCu nanodendrites exhibit efficient catalytic activity toward the methanol oxidation reaction (MOR). Particularly, the Pt₁Cu₁ nanodendrites exert 4.6× increase in the specific activity and 3.8× increase in the mass activity compared to the commercial Pt/C catalyst. The mechanism of the enhancement was comprehensively studied. The enhanced catalytic activities can be ascribed to the high index surface of the branched structure and the electronic effect between the alloy metals. Specifically, the addition of Cu downshifts the binding energy of Pt, increasing the CO-tolerance ability of PtCu nanodendrites and, hence, improves their MOR activities. Moreover, the PtCu nanodendrites display better stability and durability for MOR compared to Pt/C. The approach can be adapted to synthesize desired Pt-based nanodendrites for various catalytic reactions.