Asphalt mixture exhibits the ability of self-healing. However, the mechanism of damage healing behavior of asphalt mixtures remains unclear. Hence, the self-healing characteristics of asphalt mixture under multiple factors was studied, which helps to select the maintenance method of asphalt pavement. In this study, the self-healing process of asphalt mixtures with various damage degrees was analyzed based on the four-point bending fatigue test. The results showed that healing time and healing temperature had a positive effect on the self-healing ability of asphalt mixtures with various damage degrees, while low temperature showed a significant adverse effect on the self-healing performance of asphalt mixtures. 100% humidity had a notable influence on the self-healing ability when sufficient healing time and healing temperature were given, which reduced the self-healing efficiency to about 15%-45%. The increase in the damage degree had a significant weakening effect on the self-healing ability of asphalt mixtures. Microcracks with excessive damage extend into macroscopic cracks, which exceed the critical width of self-healing, resulting in failure to heal. In this case, external intervention is needed to improve the self-healing efficiency of the asphalt mixture with the help of other means to enhance the healing performance, and then partially restore the service performance of the pavement.