Developing new high-entropy rare-earth zirconate (HE-RE₂Zr₂O₇) ceramics with low thermal conductivity is essential for thermal barrier coating materials. In this work, the average atomic spacings, interatomic forces, and average atomic masses of 16 rare-earth elements occupying the A site of the cubic A₂B₂O₇ crystal structure were calculated by density functional theory. These three physical qualities, as vectors, characterize the corresponding rare-earth elements. The distance between two vectors quantitatively describes the difference between two rare-earth elements. For greater differences between two rare-earth elements, the disorder degree of HE-RE₂Zr₂O₇ is greater, and therefore, the thermal conductivity is lower. According to the theoretical calculations, the thermal conductivity of the ceramics gradually increases in the order of (Sc_0.2Y_0.2La_0.2Ho_0.2Yb_0.2)₂Zr₂O₇, (Sc_0.2Ce_0.2Nd_0.2Eu_0.2Gd_0.2)₂Zr₂O₇, (Sc_0.2Y_0.2Tm_0.2Yb_0.2Lu_0.2)₂Zr₂O₇, and (Sc_0.2Er_0.2Tm_0.2Yb_0.2Lu_0.2)₂Zr₂O₇. Using the solution precursor plasma spray method and pressureless sintering method, four types of HE-RE₂Zr₂O₇ powder and bulk samples were prepared. The samples all showed a single defective fluorite structure with a uniform distribution of the elements and a stable phase structure. The thermal conductivities of the sintered HE-RE₂Zr₂O₇ bulk samples ranged from 1.30 to 1.45 W·m⁻¹·K⁻¹ at 1400 °C, and their differences were consistent with the theoretical calculation results. Among the ceramics, (Sc_0.2Y_0.2La_0.2Ho_0.2Yb_0.2)₂Zr₂O₇ had the lowest thermal conductivity (1.30 W∙m⁻¹∙K⁻¹, 1400 °C), highest thermal expansion coefficient (10.19×10⁻⁶ K⁻¹, 200–1400 °C), highest fracture toughness (1.69±0.28 MPa∙m^1/2), and smallest brittleness index (3.03 μm^−1/2). Therefore, (Sc_0.2Y_0.2La_0.2Ho_0.2Yb_0.2)₂Zr₂O₇ is considered to be an ideal candidate material for next-generation thermal barrier coating applications.