Copyright © 2020 American Chemical Society. Multicomponent 3d transition-metal nanoparticles supported on Al2O3 were prepared using a complex polymerization process and a post H2-reduction treatment at 900 °C. Catalysts in a binary system were divided into two groups: single-phase alloys (NiCu and FeNi) and immiscible two-phase mixtures (FeCu and CoCu), whereas ternary (FeNiCu and CoNiCu) and quaternary (FeCoNiCu) catalysts produced single-alloy nanoparticles. The ternary and quaternary alloy catalysts achieved high NO reduction in a stoichiometric NO-CO-C3H6-O2 reaction under wet conditions (5% H2O), which simulates automotive three-way catalysis (TWC). In contrast, the activity of unary and binary systems of these metal elements significantly deteriorated in the presence of H2O. Cu-based metal catalysts are efficient for NO reduction, but they are easily deactivated by oxidation to less active oxides in the presence of O2 and/or H2O. The superiority of the multinary alloy catalysts is a result of the higher stability and regenerability of the metallic Cu species. Therefore, increasing the number of metal elements in alloy nanoparticles can provide a phase stabilization against oxidation under TWC conditions.