We aimed to analyze the association between food insecurity (FI) and academic performance in university students, including mental health and sleep quality (SQ), in an association model. A cross-sectional design included university students (n = 466, 72.5% women) from Mexico. We applied the Latin American and Caribbean Food Security Scale, the Depression Anxiety and Stress Scale (DASS-21), and the Pittsburgh Sleep Quality Index. Students self-reported their academic grading (AG) and perceptions about their academic performance. Spearman's rho and multiple logistic regression models were used. Almost half (47%) experienced some level of FI. The median AG was 95. AG was not significantly (p > 0.05) correlated with FI, nor with depression, anxiety, stress, and SQ. Considering mental health and SQ, moderate/severe FI remained significantly associated with perceived overall progress in college (OR: 2.96; 95%CI: 1.49, 5.88) and attendance to classes (OR:3.14; 95%CI: 1.19, 8.28) as poor or regular, and it was positively related to perceiving difficulties in completing their studies (OR:2.75; 95%CI: 1.43, 5.29). Stress, anxiety, depression symptoms, and poor SQ were also significantly associated with poor/regular perception of academic performance. These findings highlight the need to address psychological and nutritional factors in university students to promote their well-being and academic success.