Particle sintering and reshaping constitute the main cause for catalyst deactivation. An atomic-scale understanding of the correlation among the catalyst structure, its support, and the gas phase under realistic reaction conditions is required for its suppression. In this study, we combined high-energy grazing incidence X-ray diffraction, in situ mass spectrometry, ex situ scanning electron microscopy, and density functional theory calculations to unravel the driving force behind the composition-dependent particle shape changes and sintering processes of alpha-Al2O3(0001)-supported Pt-Pd alloy nanoparticles under realistic reaction conditions for CO oxidation. We find that pure Pt and Pt-rich particles, initially kinetically trapped in metastable flat particle shapes, undergo a strong reaction-induced height increase to adopt a more stable, theoretically predicted compact equilibrium shape. Contrarily, Pd-rich particles prove to be more resistant against shape changes, since they exhibit already a shape close to equilibrium. We thus conclude that the observed initial deviations in particle shape from the theoretical predictions are due to kinetic limitations during growth. Our data provide information on the segregation state of the alloy particles, indicating a Pt core and Pd shell structure under strongly reducing conditions and the alloying of Pt and Pd under the reaction conditions for CO oxidation close to stoichiometry.