Background: Low food security and poor mental health are a persistent concern for college students. Objective: Examine how food security and mental health are associated with college student's grade point average (GPA). Methods: American College Health Association (ACHA)-National College Health Assessment III survey data Spring 2020 of students from 75 US universities (n = 48,103) were utilized to examine relationships among mental health, food security and academic performance (GPA). Results: The majority of the population self-reported high food security (58.3%) and moderate psychological distress (50.8%). Very low food security ([beta] = -0.523, OR = 0.59, p < 0.001) and moderate psychological distress ([beta] = -0.19, OR = 0.83, p < 0.001) were inversely associated with high GPA. Reduced food security was associated with worse mental health measures. Conclusions: Food security and mental health are negatively associated with GPA. To improve student success, universities must enhance services that address food insecurity and mental health.