The CMAS corrosion behavior of a novel high entropy material (Nd0.2Gd0.2Y0.2Er0.2Yb0.2)2Zr2O7 with thermal conductivity of 1.215 W·m−1·K−1 was investigated. Results show that a dense layer composed of apatite type RE8Ca2(SiO4)6O2 phase and RE/Ca-ZrO2 forms in front of the reaction layer, which dramatically decreases the infiltration rate of CMAS from 20 to 5.3 µm/h at 1300 °C. Moreover, the elements with a larger ion radius are easier to form apatite type phase to slow down the further infiltration of CMAS. This study reveals that the high entropy (Nd0.2Gd0.2Y0.2Er0.2Yb0.2)2Zr2O7 ceramic is a promising candidate for TBCs with extreme resistance to CMAS corrosion.