This study tested a longitudinal model of religious social support as a potential mediator of the relationship between religious beliefs and behaviors, and multiple health-related outcomes (e.g., depressive symptoms, functioning, diet, alcohol use, cancer screening). A national probability sample of African Americans enrolled in the religion and health in African Americans study completed three waves of telephone interviews over a 5-year period (N = 766). Longitudinal structural equation models indicated that religious behaviors, but not beliefs, predicted the slowing of a modest overall decline in positive religious social support, while negative interactions with congregational members were stable. Positive religious support was associated with lower depressive symptoms and heavy drinking over time, while negative interaction predicted increases in depressive symptoms and decreases in emotional functioning. Positive religious support mediated the relationship between religious behaviors and depressive symptoms and heavy drinking. Findings have implications for mental health interventions in faith-based settings.