Imaging plays a crucial role in the diagnosis, prognosis and follow-up of traumatic brain injury. Whereas computed tomography plays a pivotal role in the acute setting, magnetic resonance imaging is best suited to detect the true extent of traumatic brain injury, and more specifically diffuse axonal injury. Post-traumatic brain atrophy is a well-known complication of traumatic brain injury. This study investigated the correlation between diffuse axonal injury detected with fluid-attenuated inversion recovery and susceptibility-weighted imaging magnetic resonance imaging, post-traumatic brain atrophy and functional outcome (Glasgow outcome scale - extended). Twenty patients with a closed head injury and diffuse axonal injury detected with fluid-attenuated inversion recovery and susceptibility-weighted imaging were included. The total volumes of the diffuse axonal injury fluid-attenuated inversion recovery lesions were determined for each subject's initial (<14 days) and follow-up magnetic resonance scan (average: day 303 ± 83 standard deviation). The different brain volumes were automatically quantified using a validated and both US Food and Drug Administration-cleared and CE-marked machine learning algorithm (icobrain). The number of susceptibility-weighted imaging lesions and functional outcome scores (Glasgow outcome scale - extended) were retrieved from the Collaborative European NeuroTrauma Effectiveness Research Traumatic Brain Injury dataset. The volumetric fluid-attenuated inversion recovery diffuse axonal injury lesion load showed a significant inverse correlation with functional outcome (Glasgow outcome scale - extended) (r = -0.57; P = 0.0094) and white matter volume change (r = -0.50; P = 0.027). In addition, white matter volume change correlated significantly with the Glasgow outcome scale - extended score (P = 0.0072; r = 0.58). Moreover, there was a strong inverse correlation between longitudinal fluid-attenuated inversion recovery lesion volume change and whole brain volume change (r = -0.63; P = 0.0028). No significant correlation existed between the number of diffuse axonal injury susceptibility-weighted imaging lesions, brain atrophy and functional outcome. Volumetric analysis of diffuse axonal injury on fluid-attenuated inversion recovery imaging and automated brain atrophy calculation are potentially useful tools in the clinical management and follow-up of traumatic brain injury patients with diffuse axonal injury.