The importance of psychological detachment during nonwork time has been emphasized, and its effect on depressive symptoms has been identified. However, the mechanism underlying this association remains to be elucidated. This study was conducted to identify the indirect role of emotional exhaustion in the association between psychological detachment and depressive symptoms and the moderating role of self-compassion in the relationship between emotional exhaustion and depressive symptoms on the basis of the recovery–engagement–exhaustion model and emotion regulation theory. Through an online survey, relevant data were collected from 727 university teachers (mean age, 37.65 ± 7.77 years; 38.5% men). Indirect and moderation effect were analyzed through structural equation modeling (Mplus). Psychological detachment was found to be associated with depressive symptoms through emotional exhaustion. Self-compassion moderated the association between emotional exhaustion and depressive symptoms. The association between emotional exhaustion and depressive symptoms was weaker among university teachers with high levels of self-compassion than among those with low levels of self-compassion. This study improves our understanding of the association between psychological detachment and depressive symptoms by identifying the emotional pathway and protective function of self-compassion. Interventions for improving mental health in work context should be designed considering psychological detachment and self-compassion to deal with work-induced emotional strain.