High rates of cognitive impairment persist in human immunodeficiency virus (HIV) infection, despite improved health outcomes and reduced mortality through widespread use of antiretroviral therapy (ART). Heavy alcohol use and cigarette smoking are potential contributors to neurocognitive impairment in people living with HIV (PLWH), yet few studies have examined their influence concurrently. Here we investigated the effects of self-reported alcohol use and smoking on learning, memory, processing speed, verbal fluency, and executive function in 124 HIV-positive men who have sex with men [age (mean ± SD) = 42.8 ± 10.4 years], engaged with medical care. All participants were heavy drinkers. Duration of HIV infection averaged 9.9 ± 7.6 years, and 92.7% were on a stable ART regimen. Participants completed a neuropsychological battery and assessment of past 30-day substance use. Average number of drinks per drinking day (DPDD) was 5.6 ± 3.5, and 33.1% of participants were daily smokers. Rates of neurocognitive impairment were the highest in learning (50.8%), executive function (41.9%), and memory (38.0%). Multiple regression models tested DPDD and smoking status as predictors of neurocognitive performance, controlling for age and premorbid intelligence. Smoking was significantly, negatively related to verbal learning (p = .046) and processing speed (p = .001). DPDD was a significant predictor of learning (p = .047) in a model that accounted for the interaction of DPDD and smoking status. As expected, premorbid intelligence significantly predicted all neurocognitive scores (ps < .01), and older age was associated with slower processing speed (ps < .01). In conclusion, smoking appears to be associated with neurocognitive functioning deficits in PLWH beyond the effects of heavy drinking, aging, and premorbid intelligence. Smoking cessation interventions have the potential to be an important target for improving functional outcomes in heavy drinking PLWH.