The association between obsessive-compulsive (OC) symptomatology and smoking is poorly understood, particularly in African Americans—a group subject to smoking- and OC-related health disparities. In a non-clinical sample of 253 African American smokers, we tested the negative reinforcement model of OC-smoking comorbidity, purporting that smokers with higher OC symptoms experience greater negative affect (NA) and urge to smoke for NA suppression upon acute tobacco abstinence. Following a baseline visit involving OC assessment, participants completed two counterbalanced experimental visits (non-abstinent vs. 16-hr tobacco abstinence) involving affect, smoking urge, and nicotine withdrawal assessment. OC symptom severity predicted larger abstinence-provoked increases in overall NA, anger, anxiety, depression, fatigue, urge to smoke to suppress NA, and composite nicotine withdrawal symptom index. African American smokers with elevated OC symptoms appear to be vulnerable to negative reinforcement-mediated smoking motivation and may benefit from cessation treatments that diminish NA or the urge to quell NA via smoking.