Introduction: A significant proportion of students with disabilities fail to reach the recommended levels of physical activity, a shortfall that may adversely impact both their academic performance and general well-being. Despite its relevance, the relationship between physical activity and academic outcomes in this population remains insufficiently explored. Objective: This study aimed to investigate the influence of recommended levels of physical activity on the academic performance of students with disabilities and to identify the primary barriers preventing their engagement in regular exercise. Methodology: A prospective longitudinal study was conducted involving 120 students with disabilities from four universities. Physical activity levels were measured using the Physical Activity Questionnaire-Disability, and barriers to activity were identified through the Barriers to Physical Activity Questionnaire. Academic performance was assessed by analyzing grade point averages and the frequency of exam retakes. Results: The study revealed a moderate positive correlation between physical activity levels and academic performance. Students classified as highly active had significantly higher grade point averages (4.1 versus 3.4) compared to their less active peers. Organizational (87.5%) and institutional (72.9%) barriers were the most frequently reported obstacles to engaging in physical activity. Discussion: The results are consistent with existing literature that highlights the academic and health benefits of regular physical activity among students. However, this study underscores the unique challenges faced by students with disabilities that require targeted interventions. Conclusions: The findings testify to the need to develop comprehensive programs to improve the physical activity of students with disabilities considering the identified barriers. © 2025 Elsevier B.V., All rights reserved.