ABSTRACT Objective To compare the common injuries of pre-high school American football quarterbacks (Pre-HS QBs) and high school American football quarterbacks (HS QBs) within the last 15 years. Methods A retrospective chart review was performed at a sports medicine clinic at a tertiary-level pediatric medical center. Pediatric and adolescent American football quarterback patients who sustained sports-related injuries were extracted. Injury status (acute vs. overuse), injured anatomic locations, injury types, and surgical status were compared by Pre-HS QBs (<14 years old) and HS QBs (14–18 years old). Results A total of 121 injuries were found in 118 male Pre-HS QBs (mean age: 12.4 ± 1.6), while 302 injuries were observed in 256 male HS QBs (mean age: 15.8 ± 1.4). Overall, nearly two-third (2/3) of injuries were acute (64.3%) while a little over one-third (1/3) of injuries were overuse in nature (35.7%), and there were no differences between Pre-HS and HS QBs (58.7% vs. 66.7%, p = 0.114). The top 3 injured anatomic locations for Pre-HS QBs were elbow (20.7%), shoulder (18.2%), and head/neck (14.0%). For HS QBs, the top 3 injured anatomic locations were shoulder (24.5%), knee (17.5%), and head/neck (15.2%). There were significant differences in proportion of elbow (20.7% vs. 10.6%, p = 0.006), hip/trunk/upper leg (10.7% vs. 3.3%, p = 0.002), and knee injuries (9.1% vs. 17.5%, p = 0.028) between Pre-HS and HS QBs. Pre-HS QBs had significantly more bony/cartilaginous/labral injuries than their older counterparts (60.3% vs. 46.3%, p = 0.009) while HS QBs experienced significantly more ligamentous injuries than Pre-HS QBs (14.2% vs. 5.8%, p = 0.015). Conclusions QB-associated injuries were distinctively different between Pre-HS and HS QBs. Future studies are warranted to investigate relatively high proportions of elbow injuries as well as bony/cartilaginous/labral injuries found in Pre-HS QBs.