The thermal barrier coatings (TBCs) are serviced in elevated thermal conditions characterized by chemo-thermo-mechanical (C-T-M) failure mechanism and multiscale failure modes. In the present work, isothermal, cyclic thermal and mechanical induced spalling tests were carried out. Since the contribution of aluminum migration in TBCs damage evolution and failure was confirmed, the C-T-M life prediction at the micro level, TGO respiratory growth process at the meso level and the C-T-M damage at the macro level have been developed and modeled. Multiscale modeling of C-T-M damage and clarification of EB-PVD TBCs (electron beam physical vapor deposition thermal barrier coatings) failure criterion provides an effective and feasible way to systematically analyze the essential mechanism of TBCs failure and quantitatively evaluate its service performance.