We examined the association between different types of prayer and depressive symptoms—with rumination and social support as potential mediators—in a sample of predominantly White, Christian, and female ambulatory cancer patients. In a cross-sectional design, 179 adult cancer outpatients completed measures of prayer, rumination, social support, depressive symptoms, and demographic variables. Type and stage of cancer were collected from electronic medical charts. Depressive symptoms were negatively correlated with adoration prayer (r = −.15), reception prayer (r = −.17), thanksgiving prayer (r = −.29), and prayer for the well-being of others (r = −.26). In the path analysis, rumination fully mediated the link between thanksgiving prayer and depressive symptoms (β for indirect effect = −.05), whereas social support partially mediated the link between prayer for others and depressive symptoms (β for indirect effect = −.05). These findings suggest that unique mechanisms may link different prayer types to lower depressive symptoms among cancer patients.