The durability evaluation of electron beam physical vapor deposited (EB-PVD) thermal barrier coating (TBC) systems is one of the critical issues in engineering applications. The interfacial toughness degradation as a function of the thickness of thermally grown oxide (TGO) was investigated through isothermal oxidation and cyclic oxidation tests for single-crystal superalloy specimens with an EB-PVD TBC. The critical strain criterion of TBC compression spalling was proposed through compression tests at room temperature according to noncontact full-field strain measurement technology and the digital image correlation (DIC) method. Based on a simplified mechanical model of TBC systems and elastic buckling theory, the interfacial damage was described by the critical compressive strain at spallation considering residual stress in the ceramic top coat (TC). The results indicated that the damage induced by cyclic oxidation is greater than that induced by isothermal oxidation at the same TGO thickness, showing additional damage induced in thermal cycles. Then, a new TBC life prediction model based on the nonlinear accumulation of oxidation damage and cyclic damage was developed, and the error between the damage prediction and the testing results was found to be no more than +/- 10%.