The life-saving effects of antiretroviral therapy (ART) in treating HIV infection are compromised by alcohol use. A growing body of research shows that both unintentional (e.g., memory lapses) and intentional (e.g., forgoing ART to avoid mixing with alcohol) contribute to ART non-adherence. Beliefs that it is harmful to mix alcohol with ART (alcohol-ART interactive toxicity beliefs) contribute to intentional non-adherence, but their role in overall adherence is not clear. This study conducted a clinic-based survey with 100 men and 193 women (mean age = 36) to examine the prevalence of alcohol-ART interactive toxicity beliefs and whether they contribute to treatment non-adherence in South Africa. One in three (36%, n = 106) participants reported no current alcohol use and 64% (n = 187) reported current alcohol use. The majority of participants, including current alcohol drinkers, endorsed beliefs that it is harmful to mix ART and alcohol, with 57% who currently drink reporting that they forgo taking ART when they are drinking. Participants reported being warned not to mix alcohol and ART from family, friends, and health care providers. In addition, 62% of participants who do not drink, as well as 36% of those who do drink, tell others not to mix alcohol and ART. Mediation modelling found that alcohol use directly predicts ART adherence, and that this relationship is partially mediated by alcohol-ART interactive toxicity beliefs. Health care providers can play a critical role in disputing interactive toxicity beliefs and encouraging patients to take ART even when they are drinking.