Preliminary evidence indicates that genetic factors associated with having a family history of neurodegenerative disease (fhNDD) may predispose an individual to persistent symptoms and poorer cognitive performance following concussion. However, no prior study longitudinally examined athletes with (+) and without (-) a fhNDD. Therefore, we aimed to compare clinical symptoms and cognitive performance of fhNDD+ and fhNDD- athletes at baseline and at multiple time points following concussion. Questionnaire data from the Concussion Assessment, Research and Education (CARE) Consortium were used to identify male athletes and cadets with (n = 51) and without (n = 102) a fhNDD (Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment, and non-Alzheimer’s dementia). All athletes completed the SCAT3 symptom checklist and ImPACT test prior to their sport season, and again within 24-48 hours of injury, at the unrestricted return-to-play, and at six months post-concussion. Compared to fhNDD-, fhNDD+ individuals demonstrated greater decrements in visual memory (relative to baseline) 24-48 hours post-injury (p < 0.05, d = 0.18). Additionally, a main effect of group was observed for impulse control. Compared to fhNDD- athletes, fhNDD+ individuals demonstrated greater decrements in impulse control, 24-48 hours post-injury, at the return to play, and at 6-month assessments (p < 0.01, d = 0.23). These findings suggest that male athletes with a fhNDD may exhibit greater decrements in cognitive performance following concussion. Although small, subtle deficits in cognitive performance may still significantly hinder day to day function in student-athletes.