Thermal barrier coatings (TBCs) reduce the surface temperature of superalloy components but may affect the mechanical properties of the substrate. This study investigates the creep-fatigue behavior of TBC-coated single-crystal superalloys under 1 s, 60 s, and 180 s dwell times. The results indicate that TBCs are beneficial at a 1 s dwell time. The comparison of fracture morphology between coated and uncoated samples showed no change in the failure mechanism due to TBCs under creep-fatigue loading. A creep-fatigue lifetime prediction method based on continuous damage mechanics was also proposed. The predicted results were all within a double dispersion coefficient, showing good agreement with the experimental results. This study provides insights into the durability of TBC-coated single-crystal superalloys under creep-fatigue loading.