The oxygen reduction reaction (ORR) has been studied on well-defined PtPd single-crystal electrodes to understand the role of the surface structure and composition in the electrocatalysis of this reaction in HClO4 and NaOH solutions. The voltammetric behavior in the supporting electrolyte shows that the inclusion of Pd in the Pt single-crystal electrodes affects the OH adsorption strength and, in a different way, is dependent on the surface orientation. OH adsorption is weakened for the (100) surfaces, whereas there is no significant change in OH adsorption strength on the (111) surfaces. Since the OH desorption step is considered the limiting step in the ORR, Pt100–xPdx(100) electrodes show a significant increase in reactivity when compared to the pure Pt(100) surface. These results are corroborated when the hydrogen peroxide reduction reaction (HPRR) is studied since its reactivity is also dependent on the OH adsorption strength. Moreover, HPRR studies have shed light on the role of hydrogen peroxide as an intermediate in the ORR, suggesting that in acidic media, H2O2 is a key intermediate, while in alkaline media, the presence of Pd avoids the formation of soluble peroxide.