Three‐way catalysis represents a pivotal technology for converting automobile exhaust pollutants into non‐toxic gases. Substituting some noble metals with transition metals is considered a promising way to reduce catalyst costs. Herein, we have investigated the catalytic potential of different configurations of Pd‐Cu catalysts prepared by impregnation (PdCu/MA), sol‐gel (PdCu‐MA), impregnation with physical mixing (Pd/Cu/MA) and sol‐gel with physical mixing (Pd/Cu‐MA) to modify the interaction of Pd/Cu and MgAl1.82Ce0.18O4 (MA) spinel in this comparative study. The different structures in these catalysts lead to different catalytic performances. PdCu/MA exhibits the best three‐way catalytic performance, which owe to the small‐sized PdCu particles with high Pd2+ content (45.3%) and optimal interaction of Pd/Cu particles and MgAl1.82Ce0.18O4 support. Furthermore, comprehensive CO‐DRIFTS, H2‐TPR, and O2‐TPD analyses discover that the metal‐support interaction is beneficial to enhance the catalytic performance in three‐way catalysis. Overall, we demonstrated that the interaction between PdCu bimetals and support can regulate the electronic state of Pd, thereby enhancing the use and efficiency of noble metals.