The present study assessed the associations between autistic traits and the reporting of alcohol use motives, positive consequences of alcohol use, appeal of drug use, and problematic substance use among college students. Despite receiving little attention in the academic literature, autism spectrum disorder (ASD) and substance use disorder (SUD) as a dual diagnosis is seen in clinical populations. As social anxiety is commonly reported by both individuals with ASD and SUD, symptoms of social anxiety were thought to enhance the relationship between autistic traits and substance use, thus serving as a moderator. College students were recruited to complete an anonymous survey, and a total of 645 participants were included in the analyses. Findings revealed that autistic traits were significantly correlated with coping drinking motives and appeal of drug use. Additionally, there was a significant interaction between autistic traits and social anxiety for social drinking motives and alcohol use positive consequences such that there were significant negative associations at low levels of social anxiety for social motives, and at low and average social anxiety for alcohol use positive consequences. Results from this study suggest a noteworthy relationship between more autistic traits and the likelihood of reporting drinking alcohol for reasons to cope (i.e., alcohol helps when you feel depressed), as well as reporting drug use as appealing. Across all analyses, social anxiety did not appear as a moderator in the hypothesized direction, as so, future research should examine other potential moderators. Furthermore, findings should inform future research to explore why drug use may be more appealing to individuals with autistic traits than alcohol use.