High-temperature damage characteristics related to the deformation behavior of Sanicro25 alloy were investigated under cyclic loading. The results show that the high mean stress can lead to creep-like deformation behavior. The increase of mean stress increased the strain rate and weakened the life. Comparatively, the increase in stress amplitude only accelerated the third-regime strain rate, leading to a decrease in life and fracture strain. Under different stress amplitudes, microcrack initiation at Z phase interfaces can be certified by observing micropore and high geometrically necessary dislocation (GND) density around Z phase. Subsequently, the increase in stress amplitude can significantly affect crack propagation. Under constant loading ( σ a =0MPa ), the recrystallization of the transgranular crack tip at the grain boundary can change the tendency of crack propagation, making crack propagation along the grain boundaries. Conversely, transgranular cracks can continue to propagate, assisted by intragranular dislocation accumulation at higher stress amplitude ( σ a =130MPa ).