The development and exploration of cathode oxides with outstanding electrocatalytic activity are critical processes aimed at achieving a decrease in the operation temperature of solid oxide fuel cells (SOFC). Herein, a novel high-entropy oxide, La0.2Pr0.2Nd0.2Sm0.2Gd0.2BaCoFeO5+δ (HEP), which incorporates five lanthanide species (La, Pr, Nd, Sm, and Gd) in the A-site of perovskite, has been specifically developed and assessed as selected cathode for intermediate-temperature SOFC. Investigations of phase structure, chemical compatibility, oxygen transport characteristics, oxygen reaction kinetic, thermal expansion, surface chemical state, conductivity, as well as CO2/Cr-durability are thoroughly performed to assess the basic physicochemical properties of the HEP cathodes. The HEP cathode possesses good operational stability, moderate thermal expansion behavior, fast oxygen transport dynamics, and superior chemical compatibility with the electrolyte. At 700 °C, the polarization resistance low to 0.072 Ω cm2 and output power density high to 332.2 mW cm−2 were obtained for the symmetrical and electrolyte-supported single cells. Furthermore, a stable current density is obtained for the single cell operating at 600 °C and 0.5 V for 100 h. Analysis of electrochemical impedance spectra (EIS) and distribution of relaxation time (DRT) data at different oxygen partial pressures reveal that the charge-transfer and oxygen ions ionization processes at intermediate frequencies present a significant limiting step in the rate of the oxygen reduction reaction. However, under realistic utilization conditions, cathodes of cells often endure irreversible performance degradation owing to the Cr deposition from interconnects or CO2 poisoning in air. Hence, the behavior of Cr and CO2 poisoning is also systematically investigated in symmetrical cell measurements; the results confirm that the HEP cathode displays good resistance to Cr and CO2 poisoning. Overall, our findings indicate that the HEP material is regarded as a favored ceramic cathode for SOFC.