Traumatic brain injury (TBI) is a pathologically heterogeneous disease, including injury to both neuronal cell bodies and axonal processes. Global atrophy of both gray and white matter is common after TBI. This study was designed to determine the relationship between neuroimaging markers of acute diffuse axonal injury (DAI) and cerebral atrophy months later. We performed high-resolution magnetic resonance imaging (MRI) at 3 Tesla (T) in 20 patients who suffered non-penetrating TBI, during the acute (within 1 month after the injury) and chronic stage (at least 6 months after the injury). Volume of abnormal fluid-attenuated inversion-recovery (FLAIR) signal seen in white matter in both acute and follow-up scans was quantified. White and gray matter volumes were also quantified. Functional outcome was measured using the Functional Status Examination (FSE) at the time of the chronic scan. Change in brain volumes, including whole brain volume (WBV), white matter volume (WMV), and gray matter volume (GMV), correlates significantly with acute DAI volume (r = -0.69, -0.59, -0.58, respectively; p <0.01 for all). Volume of acute FLAIR hyperintensities correlates with volume of decreased FLAIR signal in the follow-up scans (r = -0.86, p < 0.001). FSE performance correlates with acute hyperintensity volume and chronic cerebral atrophy (r = 0.53, p = 0.02; r = -0.45, p = 0.03, respectively). Acute axonal lesions measured by FLAIR imaging are strongly predictive of post-traumatic cerebral atrophy. Our findings suggest that axonal pathology measured as white matter lesions following TBI can be identified using MRI, and may be a useful measure for DAI-directed therapies.