We examined cross-sectional associations of health literacy (HL) with smoking and other established health indicators among 1,467 African American adults. Data emanated from a longitudinal cohort study designed to investigate cancer risk factors among church-going African American adults. We conducted linear and logistic regression analyses to assess associations between HL and health indicators. HL was assessed using an established single-item screening question. Outcomes included indicators of poor physical health (cigarette smoking, self-rated general and physical health) and mental health (self-rated mental health, depressive symptoms, perceived stress). Nearly 19% of participants had low HL. Low HL was significantly associated with current smoking, poorer self-rated general and physical health, and higher perceived stress (ps < .05) even after we controlled for demographic variables (i.e., age, gender, relationship status) and indicators of socioeconomic status (i.e., education, income, insurance status). Low HL appears to be an independent risk factor for smoking and other indicators of poor physical and mental health in a large sample of African American adults. Future directions and clinical implications are discussed.