Traumatic brain injury (TBI, neurotrauma) is an urgent biomedical concern with high prevalence and mortality risks. Probing TBI mechanisms in traditional (e.g., rodent) animal models is often complicated by the complexity and limited regenerative potential of rodent brain. Here, we present a zebrafish (Danio rerio) model of telencephalic stab wound injury, and assess behavioral and molecular consequences of TBI. Four days following the injury, adult zebrafish displayed hypolocomotion in the novel tank test and impaired working memory in the Y-maze test, paralleling behavioral deficits in rodent models and human TBI patients. Molecular analysis of key genes involved in the inflammatory response and cell death pathways revealed a remarkable upregulation of the interferon-stimulated gene 15 (isg15), a biomarker for neuronal injuries, in the traumatized telencephalon. Furthermore, norepinephrine levels in whole-brain tissue significantly declined following TBI, likely contributing to the observed cognitive deficits and further implicating neurotransmitter dysregulation in TBI pathogenesis.