Supported alloy nanoparticles are prevailing alternative low-cost catalysts for both heterogeneous and electrochemical catalytic processes. Gas molecules selectively interacting with one metal element induces a dynamic structural change of alloy nanoparticles under reaction conditions and largely controls their catalytic properties. However, such a multicomponent dynamic-interaction-controlled evolution, both structural and chemical, remains far from clear. Herein, by using state-of-the-art environmental TEM, we directly visualize, in situ at the atomic scale, the evolution of a AuCu alloy nanoparticle supported on CeO2 during CO oxidation. We find that gas molecules can "free" metal atoms on the (010) surface and form highly mobile atom clusters. Remarkably, we discover that CO exposure induces Au segregation and activation on the nanoparticle surface, while O2 exposure leads to the segregation and oxidation of Cu on the particle surface. The as-formed Cu2O/AuCu interface may facilitate CO-O interaction corroborated by DFT calculations. These findings provide insights into the atomistic mechanisms on alloy nanoparticles during catalytic CO oxidation reaction and to a broad scope of rational design of alloy nanoparticle catalysts.