Black women are at high risk of discrimination due to intersectionality as well as cognitive impairment in later life. However, we do not yet know enough about the association between discrimination and cognition in this population or which protective factors may buffer the adverse effect of discrimination on cognitive outcomes. The present study aimed to determine whether discrimination was associated with adverse cognitive outcomes (i.e., episodic memory, processing speed, working memory) in midlife Black women and whether social support and religiosity/spirituality were significant moderators of the association between discrimination and cognitive outcomes. The present study was conducted using data from 669 midlife Black women from the Study of Women’s Health Across the Nation (SWAN). Results indicated that there was a high prevalence of spirituality and a low incidence of discrimination exposure in the sample. Using structural equation modeling, discrimination was not associated with cognition, nor was social support a significant moderator of the association between discrimination and cognition. Spirituality was a significant moderator of the association between discrimination and cognition such that, for women with greater spirituality, greater discrimination was associated with better processing speed. These surprising results suggest that there is heterogeneity in how discrimination is associated with cognition in midlife Black women. There is an opportunity to better incorporate spirituality into clinical interventions to promote cognitive health for Black women.