<p>Academic disruptions are associated with the emergence of schizophrenia spectrum symptoms and substance use. In particular, being in a college environment may present with stressors that contribute to elevations in sub-clinical risk indicators for schizophrenia deemed schizotypy and may influence functional outcomes. However, there is limited research examining how sub-clinical symptoms influence college academic performance. In the current study, undergraduate students (<i>n</i> = 366) provided baseline data and permission for academic indicators to be tracked over time. Participants completed baseline demographic, schizotypy, and substance use self-reports. Academic performance indicators including grade-point averages (GPA), total credits earned, attempted vs. completed credits ratio, and graduation rates were recorded over a 7-year period. It was anticipated that elevations in levels of schizotypy and substance use would independently predict poorer academic functioning. The influence of gender was also examined amongst schizotypy, substance use, and academic performance variables. Our hypotheses were partially supported. Mixed model analysis suggested that time, gender, and nicotine use had significant effects, with nicotine use contributing to lower GPA over time. While schizotypy and its subscales did not contribute significantly in the mixed model analysis, gender-based correlations demonstrated unexpected positive relationships between schizotypy and GPA for males. These preliminary findings suggest that nuanced relationships may exist between schizotypy, substance use, and academic functioning. Additional research is needed to determine if these unusual findings can be replicated in different samples across the schizophrenia spectrum and to further clarify the role of gender in academic functioning differences.</p>