Pt-Ir nanocubes with (100)-terminated facets were synthesized for the first time and their unusual high electrocatalytic activity for a model reaction (i.e., ammonia oxidation) was reported. The key parameters in controlling the shape of the PtIr nanocubes were systematically investigated by transmission electron microscopy (TEM). The electrocatalytic activities of the prepared Pt-Ir and pure Pt nanoparticles (NPs) were characterized by cyclic voltammetry (CV). The results showed that the amount of W(CO) 6 and the volume ratio of oleylamine and oleic acid play a significant role in the development of well-defined Pt-Ir nanocubes. The resultant Pt-Ir nanocubes exhibit (100) orientation, which has been confirmed by not only the structural characterization results from high-resolution TEM (HRTEM) and X-ray diffraction (XRD) but also hydrogen desorption profiles obtained from the CV measurements in H 2 SO 4 solution. Lattice contraction of the Pt-Ir nanocubes were suggested by HRTEM and XRD measurements, and the electronic interactions between Pt and Ir in the Pt-Ir nanocubes were demonstrated by X-ray photoelectron spectroscopy. The Pt-Ir nanocubes show higher specific activity than pure Pt nanocubes and much higher specific activity than the polycrystalline Pt-Ir NPs. The much improved specific activity of the Pt-Ir nanocubes could be attributed to the reason that the introduction of Ir in the Pt-Ir nanocubes largely maintains the highly active Pt (100) sites and thus a positive synergistic effect through the addition of Ir to Pt could be achieved due to the possible bifunctional mechanism and the electronic effect.