Brain damage is a serious economic and social burden. Contact sports such as American football, are one of the most common sources of concussions. The biomechanical response of the head–helmet system caused by dynamic loading plays a major role. The literature has focused on measuring the resultant kinematics that act on the head and helmet during tackles. However, few studies have focused on helmet validation tests, supported by recent findings and emerging numerical approaches. The future of helmet standards could benefit from insights at the level of injury mechanisms, using numerical tools to assess the helmets. Therefore, in this work, a numerical approach is employed to investigate the influence of intracranial pressure (ICP) on brain pathophysiology during and after helmeted impacts, which are common in American football. The helmeted impacts were performed at several impact locations according to the NOCSAE standard (configurations A, AP, B, C, D, F, R, UT). In order to evaluate the ICP levels, the αHEAD finite element head and brain model was combined with a Hybrid III-neck structure and then coupled with an American football helmet to simulate the NOCSAE impacts. In addition, the ICP level was analyzed together with the resulting HIC value, since the latter is commonly used, in this application and others, as the injury criterion. The obtained results indicate that ICP values exceed the common threshold of head injury criteria and do not correlate with HIC values. Thus, this work raises concern about applying the HIC to predict brain injury in American football direct head impacts, since it does not correlate with ICP predicted with the FE head model.