Sc was doped into Gd2Zr2O7 for expanding the potential for thermal barrier coating (TBC) applications. According to first-principles calculation, the solid solution mechanism of Sc in Gd2Zr2O7 lattice was revealed, i.e., Sc first occupies the lattice interstitial sites followed by substituting for Gd, and the interstitial Sc concentration is less than 11.11%. By considering the mechanical and thermophysical properties comprehensively, the optimum Sc doping content was determined to be 16.67%, and this composition was selected to produce TBCs by air plasma spraying with YSZ as a bottom ceramic coating (Gd-Sc/YSZ TBC). After sintering at 1400 ℃ for 100 h, Gd-Sc coatings remain phase and structural stability indicative of excellent sintering resistance. By thermal cycling tests, Gd-Sc TBCs fails due to the low toughness and the interface reaction between Gd-Sc and boding coatings, while Gd-Sc/YSZ TBCs exhibit much longer thermal cycling lifetime, and the failure mode is YSZ coating cracking.