We characterized traumatic brain injury (TBI) and studied its associations with mental and physical health in a community cohort of homeless and vulnerably-housed individuals. Methods: Detailed mental and physical health structured interviews, neuropsychological testing, and multimodal MRI were performed on 283 participants. Two traumatic brain injury (TBI) participant groups were defined for primary analyses: those with a self-reported history of TBI and those with MRI evidence of TBI. Results: By self-report, 174 participants (61.5%) reported a previous head injury (symptomatic or asymptomatic), with 100 (35.3%) experiencing symptoms consistent with TBI (any post-injury loss of consciousness, confusion or memory loss). Persons self-reporting TBI had poorer current mental and physical health, more ongoing neurological symptoms, and a higher rate of mood disorders, compared with those with no head injury. The presence of a mood disorder, a TBI history, and an interaction between these factors contributed to lower mental health. There was evidence of traumatic brain injury in 20 participants (6.9%) on clinical MRI sequences. These participants had globally lower cortical grey matter volumes and lower white matter fractional anisotropy (FA) values. Neurocognitive test scores positively correlated with both FA and cortical grey matter volumes in participants with MRI evidence of trauma. Conclusion: Previous TBI is associated with poorer mental and physical health in homeless and vulnerably-housed individuals and interacts with mood disorders to exacerbate poor mental health. Focal traumatic lesions evident on MRI are associated with diffusely lower grey matter volumes and white matter integrity, which predict cognitive functioning.