Objective Traumatic Brain Injury (TBI) is a brain dysfunction caused by an external force impact or penetration to the head. In recent years, the incidence and associated mortality of TBI have been increasing annually, posing significant challenges to the healthcare system and the socio-economic environment. This study aims to investigate the impact of sex on the incidence, clinical presentation, treatment, and prognosis of TBI patients. Methods A retrospective analysis was conducted on the clinical data of 1,218 TBI patients hospitalized in the Department of Neurosurgery at Northern Theater General Hospital from 2012 to 2023. The data included age, sex, cause of injury, Glasgow Coma Scale (GCS) score, injury type, and prognosis. Chi-square tests and logistic regression analysis were used to evaluate the impact of sex on the prognosis of TBI patients. Results The results showed that the proportion of male patients was significantly higher than that of female patients (80.0% vs. 20.0%, P<0.001), and the average age of female patients was higher than that of male patients (54.28 years vs. 50.04 years, P = 0.006). Traffic accidents were the main cause of injury for female patients, whereas falls from heights were the primary cause for male patients. Multivariate logistic regression analysis revealed that age, traffic accidents, GCS score ≤ 8, subdural hematoma, and epidural hematoma were independent predictors of mortality in TBI patients. Conclusion Sex significantly impacts the incidence and clinical characteristics of TBI. Male patients have a higher incidence of TBI, while female patients are generally older and primarily injured due to traffic accidents. Age, traffic accidents, low GCS scores, subdural hematoma, and epidural hematoma are independent predictors of mortality in TBI patients. Therefore, different prevention and treatment strategies should be developed for TBI patients based on their sex and age to improve prognosis and reduce mortality rates.