Objective: ADHD symptoms are highly prevalent among university students. These symptoms, particularly the inattentive cluster, predispose students to poorer academic performance and worse academic adjustment. Moreover, ADHD symptoms are often comorbid with other common mental disorders; this comorbidity also leads to poor outcomes. South African students often have fewer resources to successfully transition to university. Hence, our longitudinal study used data from a sample of South African first-year undergraduate students to investigate (a) associations between ADHD symptoms and academic performance/adjustment, (b) separate influences of the inattentive and hyperactivity-impulsivity clusters on academic performance/adjustment, and (c) the influence of the combination of ADHD and psychiatric comorbidities on academic performance/adjustment. Method: We collected data three times through the first semester of 2023. Predictors within our regression models included sociodemographic variables, psychological variables (self-reported symptoms of ADHD, depression, anxiety, and risky alcohol use), and high school academic performance. Outcomes were first-semester GPA and self-reported academic adjustment (magnitude of change across the semester and overall adjustment at the end of the semester). Results: Analyses showed that, unlike academic performance (N = 506), magnitude of change in academic adjustment (N = 180) was significantly predicted by ADHD symptoms and the combination of ADHD (p = 0.02), depression (p < 0.001), and anxiety symptoms (p = 0.01). Inattentive ADHD symptoms predicted both academic performance and magnitude of change in academic adjustment. Conclusions: Our findings suggest that the presence of ADHD symptoms (both with and without other common mental disorders) is associated with a smaller magnitude of academic adjustment, and that the presence of inattentive symptoms of ADHD is associated with both poorer academic performance and smaller magnitude of academic adjustment. These findings are significant in informing future interventions targeting the academic outcomes of first-year university students.