The formic acid oxidation reaction (FAOR) represents an important class of small organic molecule oxidation and is central to the practical application of fuel cells. In this study, we report the fabrication of Ir(IV)-doped PdAg alloy nanodendrites with sub-5 nm branches via stepwise synthesis in which the precursors of Pd and Ag were co-reduced, followed by the addition of IrCl3to conduct an in situ galvanic replacement reaction. When serving as the electrocatalyst for the FAOR in an acidic medium, Ir(IV) doping unambiguously enhanced the activity of PdAg alloy nanodendrites and improved the reaction kinetics and long-term stability. In particular, the carbon-supported PdAgIr nanodendrites exhibited a prominent mass activity with a value of 1.09 A mgPd−1, which is almost 2.0 times and 2.7 times that of their PdAg and Pd counterparts, and far superior to that of commercial Pt/C. As confirmed by the means of the DFT simulations, this improved electrocatalytic performance stems from the reduced overall barrier in the oxidation of formic acid into CO2during the FAOR and successful d-band tuning, together with the stabilization of Pd atoms. The current study opens a new avenue for engineering Pd-based trimetallic nanocrystals with versatile control over the morphology and composition, shedding light on the design of advanced fuel cell electrocatalysts.