Religious participation and spirituality are linked to good mental health. However, clergy may experience more depression than is observed in the general population, which may be due in part to high job strain. The objectives of this study were to identify distinct longitudinal trajectories of depressive symptoms in clergy and to identify variables associated with each course. The sample was 1172 clergy who were followed for up to 66 months. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-8), which was administered approximately every 6 months. Latent class trajectory analysis was conducted for group identification, and a 3-class trajectory model fit the data best. Class 1 (38% of the sample) had minimal or no depressive symptoms over time, class 2 (47%) had chronic mild symptoms, and class 3 (15%) had persistent moderate/severe symptoms. Occupational distress was significantly associated with trajectory class. The odds of being in either the chronic mild or the persistent moderate/severe depressive symptom class were significantly higher for those who were female, for those with fair/poor self-rated health, for those with more perceived financial or occupational stress, for those with lower levels of perceived emotional support, and/or for those with lower levels of spiritual well-being. The class exhibiting resilience to depressive symptoms had higher levels of perceived support and spiritual well-being as well as lower levels of perceived financial and occupational stress. A substantial percentage of clergy, and possibly people in similar helping occupations, may experience significant levels of depressive symptoms that do not remit over time. These individuals may benefit from treatments that address work-related coping.