High-entropy engineering is an emerging strategy to enhance material properties beyond their individual components. In this study, we synthesized a high-entropy spinel oxide cathode material, Ni(Fe0.2Mn0.2Co0.2Cr0.2Ni0.2)2O4, for solid oxide fuel cells (SOFCs) using a solution combustion method. The material exhibits a spinel structure with diverse surface metal valence states and a high concentration of oxygen vacancies. Density functional theory calculations reveal the B-site high-entropy design can significantly improve the oxygen adsorption capability. Electrochemical tests demonstrate that Ni(Fe0.2Mn0.2Co0.2Cr0.2Ni0.2)2O4 has superior conductivity and oxygen reduction activity compared to binary spinel oxides. An anode-supported SOFC with Ni(Fe0.2Mn0.2Co0.2Cr0.2Ni0.2)2O4 cathode achieved a peak power density of 583 mW cm-2 at 800 °C. Impedance and relaxation time distribution (DRT) analyses indicate that the oxygen molecular dissociation and oxygen atom diffusion dominates the cathode polarization. This study demonstrates that high-entropy engineering of the B-site in spinel oxides is a promising strategy to optimize cathode performance for SOFCs.