Controlling the dynamic structural evolution of supported metals under reaction conditions is essential for developing optimal catalysts that enhance reactor efficiency and simplify reaction processes. Herein, we show that the reducibility of the metal-oxide support governs the compositional dynamics in supported Pt/Cu bimetallic nanoparticles for a probe oxidation reaction. X-ray absorption spectroscopy reveals that, on an alumina support, the particles primarily expose oxidized Cu on the surface. On a manganese oxide support, Pt is oxidized and exposed. Density functional theory calculations reveal that charge transfer from Pt to Mn increases the oxophilicity of Pt while simultaneously preventing electron transfer from Cu to Pt, thus hindering Cu oxidation. This dynamic behavior enhances both the rate and stability of the Pt/Cu phase supported on manganese oxide. Our findings demonstrate how metal-support interactions drive the reactivity of the supported phase by controlling its surface composition.