The search for resilience factors that could minimize the transition from burnout to depression may offer a valuable approach for depression prevention. The present study investigated whether humor could be such a potential resilience factor in two independent studies. In study 1 (n = 58, students), we used a performance-based approach integrating linguistic and psychometric methods to investigate whether the ability to produce humor in positive reappraisal moderates the association between burnout and depressive symptoms in university students. To examine the generalizability of the results from study 1, study 2 (n = 932) explored whether the level of humor as a habit (i.e., self-rated playfulness) also moderates this association in a population-based sample. In both studies, the burnout sub-dimensions of emotional exhaustion and cynicism were correlated with depressive symptoms. In study 1, this association was evident only in students with poorer ability to create humor in terms of quality (wittiness). In study 2, the association between emotional exhaustion and depressive symptoms was similarly moderated by the self-rated habit to create humor (i.e., playfulness). Possible implications of these results for the role of humor in reducing the relationship between burnout symptoms and depression, thereby supporting depression prevention, are discussed.