We examined prospective associations between religiousness/spirituality (R/S; i.e., service attendance, R/S identity, R/S coping, spirituality) and all-cause mortality in the Midlife in the United States (MIDUS) sample, including whether having a purpose in life and positive social support are indirect pathways through which R/S predicts mortality. We examined service attendance and a composite of R/S identity, R/S coping, and spirituality from the baseline wave (1995–1996; n = 6120 with complete data), purpose in life and positive social support from the second wave (2004–2006), and vital status through 2020 (n = 1711 decedents). Cox regression models showed that attending religious services more than weekly and approximately weekly was associated with a lower mortality risk compared to never attending in the adjusted models (>weekly vs. never, HR (95% CI) = 0.72 (0.61, 0.85); weekly vs. never, HR (95% CI) = 0.76 (0.66, 0.88)). The R/S composite was also associated with lower mortality risk in the adjusted models (HR (95% CI) = 0.92 (0.87, 0.97)). Indirect effects from R/S to mortality via purpose in life and positive social support were significantly different from zero. These findings highlight the importance of multidimensional aspects of R/S for population health and point to purpose in life and positive social support as underlying pathways between R/S and mortality.