This study clarified longitudinal relations of spirituality and religiosity with depression. Spirituality's potential emphasis on internal (e.g., intrapsychic search for meaning) versus religiosity's potential emphasis on external (e.g., engagement in socially-sanctioned belief systems) processes may parallel depression-linked cognitive-behavioral phenomena (e.g., rumination and loneliness) conceptually. Thus, this study tested the hypothesis that greater spirituality than religiosity, separate from the overall level of spirituality and religiosity, predicts longitudinal increases in depression. A national sample of midlife adults completed diagnostic interviews and questionnaires of spiritual and religious intensity up to three times over 18 years. In time-lagged multilevel models, overall spirituality plus religiosity did not predict depression. However, in support of the hypothesis, greater spirituality than religiosity significantly predicted subsequent increases in depressive symptoms and risk for major depressive disorder (odds ratio = 1.34). If replicated, the relative balance of spirituality and religiosity may inform depression assessment and prevention efforts.