In this study, 16 mol% CeO2–2 mol% Sc2O3 co-stabilized ZrO2 (4S16CZ) coating was prepared by atmospheric plasma spraying (APS) technology. Parameters related to the application of 4S16CZ as a thermal barrier coatings (TBCs) were studied, including high-temperature stability, thermal insulation performance, coefficient of thermal expansion (CTE), thermal shock behavior and CaO-MgO-Al2O3-SiO2 (CMAS) resistance. After heat treatment at 1400 °C for 100 h, the 4S16CZ coating maintained a single non-transformable tetragonal phase (t'), exhibiting excellent high-temperature stability. Additionally, at the test temperatures (25 °C–1000 °C), the thermal conductivity of the 4S16CZ coating ranged from 0.79 W/(m·K) to 1.02 W/(m·K), lower than that of the ZrO2 coating stabilized by 7.6 wt% Y2O3 (YSZ, 0.88–1.13 W/(m·K)), The CTE of the 4S16CZ coating was from 8.3 × 10−6 K−1 to 11.2 × 10−6 K−1, which was comparable to the YSZ. Moreover, the thermal shock behaviors of 4S16CZ TBCs and 4S16CZ/YSZ TBCs were evaluated at 1050 °C. The thermal durability of the 4S16CZ/YSZ TBCs was higher than that of 4S16CZ TBCs due to the buffering effect of the YSZ layer. The main reasons for the failure of both TBCs were the oxidation of the bond coat, thermal mismatch stress, low fracture toughness and sintering effects. In CMAS isothermal corrosion tests, CMAS exhibited low wettability on the 4S16CZ coating. Compared with the YSZ coating, the 4S16CZ coating showed better resistance to CMAS attacks.