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The mechanisms by which head injury induces acute concussion and chronic sequelae are not known. We examined postmortem brains from young athletes in the subacute period after closed-head concussive impact injury and found parenchymal contusion, myelinated axonopathy, microvasculopathy, neuroinflammation, neurodegeneration, and phosphorylated tauopathy consistent with early chronic traumatic encephalopathy (CTE). We developed a biofidelic mouse model of closed-head impact injury that induces non-skull-deforming head acceleration and transient signs of concussion in non-anesthetized C57BL/6 mice. Mice subjected to lateral head impact exhibited contralateral limb and trunk weakness, impaired gait and balance, and locomotor abnormalities that recapitulate neurological signs and temporal course of acute concussion in humans. Neurological function rapidly returned to baseline; however, CTE-linked pathology, phosphorylated tau proteinopathy, and functional sequelae persisted long after recovery. We used an albumin-binding gadolinium contrast agent to demonstrate in vivo blood-brain barrier disruption that upon histological analysis colocalized to brain regions exhibiting neuroinflammation and CTE-linked tau proteinopathy. Notably, concussion did not correlate with markers of CTE pathology or functional sequela. [ABSTRACT FROM AUTHOR]