This study proposed a multiaxial variable temperature and amplitude damage assessment model to predict the variable temperature and amplitude fatigue life of high-temperature alloys, which are often subjected to varying multiaxial mechanical and temperature loads. To validate the proposed model, seven variable temperature and amplitude fatigue tests were conducted on GH4169 nickel-based high-temperature alloy. The proposed model shows good accuracy and reliability in predicting the lifetime of high-temperature alloy components under multiaxial mechanical and temperature loads.