Chronic Traumatic Encephalopathy (CTE) is an established neurodegenerative disease that is closely associated with exposure to repetitive mild traumatic brain injury (mTBI). The mechanisms responsible for its complex pathological changes remain largely elusive, despite a recent consensus to define the neuropathological criteria. Here, we provide details of a novel protocol to develop a model of CTE in fruit fly Drosophila melanogaster in an attempt to identify the key genes and pathways that lead to the characteristic hyperphosphorylated tau accumulation and neuronal death in the brain. The advantage of this protocol is that adjustable-strength impacts are delivered directly to the fly head to inflict mild closed injury, subjecting the head to rapid acceleration and deceleration. The less labor- and cost-intensive animal care, short life span, and extensive genetic tools make the fruit fly ideal to study CTE pathogenesis and make it possible to perform large-scale, genome-wide forward genetic and pharmacological screens.