Anxiety sensitivity (AS)-fearfulness of anxiety symptoms-has been implicated in the etiology of emotional disorders (e.g., depressive and anxiety disorders) and linked to cigarette smoking and other substance use (SU). However, studies examining AS in relation to SU primarily have been conducted with racially/ethnically heterogeneous or mostly European American samples. Hence, this cross-sectional study involving secondary analysis of baseline data focused on investigating associations of AS with cigarette smoking and other SU in a sample of 630 non-treatment-seeking African American smokers (37.3% female; M age = 49.6 years; M cigarettes smoked per day = 15.4). After screening out individuals with non-nicotine substance dependence, participants reported their demographics, AS, dysphoria symptoms (i.e., depression and anxiety symptoms), and SU. In regression analyses controlling for dysphoria symptoms, age, education level, income level, and years of regular smoking, AS was positively associated with tobacco withdrawal severity (β = .12, p = .007), overall smoking motives (β = .17, p < .001), alcohol use problems (β = .12, p = .005), and other (non-nicotine, nonalcohol) SU problems (β = .16, p < .001). Though lacking the passage of time between assessments needed to provide strong evidence of mediation, unplanned analyses further revealed indirect associations of AS with several SU variables through dysphoria symptoms. Current findings are consistent with those found in prior samples and suggest that AS is similarly related to SU in African Americans, who may benefit from interventions that have been helpful in improving AS, dysphoria symptoms, and SU in other groups. (PsycInfo Database Record (c) 2020 APA, all rights reserved).