In this work, we have successfully fabricated a novel high-entropy rare-earth zirconate (La0.2Nd0.2Sm0.2Gd0.2Yb0.2)2Zr2O7 (5RE2Zr2O7) ceramics and its counterparts by using a new high-speed grinding strategy combined with typical solid-state reaction method. The X-ray diffraction (XRD) and Raman spectroscopy analysis indicated that the as-prepared 5RE2Zr2O7 ceramics performed single-phase defect fluorite-type structures with highly sintering resistant and excellent thermal stability. The possibility of formation of 5RE2Zr2O7 was verified via first-principles calculations. Meanwhile, the phase structure, thermophysical and mechanical properties of the samples were systematically investigated. The results showed that the 5RE2Zr2O7 ceramics demonstrated lower thermal conductivity (0.9-1.72 W·m-1·K-1) and higher thermal expansion coefficients (10.9 × 10-6 K-1 at 1273 K) than its counterparts. Furthermore, the 5RE2Zr2O7 ceramics presented outstanding mechanical properties including large Young’s modulus (186-257 GPa), higher fracture toughness and lower brittleness index than that of YSZ. Therefore, in view of various excellent properties, the as-prepared 5RE2Zr2O7 ceramics possess great potential for applications in the field of thermal barrier coatings.