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Introduction: Traumatic brain injury is a major global public health problem causing substantial mortality among the adult population. Hence, this study aimed to determine the predictors of mortality among adult traumatic brain injury patients in Felegehiwot Comprehensive Specialized Hospital in Northwest Ethiopia during 2020. Methods: A retrospective cohort study was conducted at Felegehiwot Comprehensive Specialized Hospital using anonymized patient data obtained from chart review. Descriptive statistics were used to summarise the patient characteristics. The Kaplan–Meier survival curve and log-rank test were used to test for differences in survival status among groups. The Cox proportional hazards regression model was used at the 5% level of significance to determine the net effect of each explanatory variable on time to death. Results: In total, 338 patients aged ≥15 years and diagnosed with traumatic brain injury were included in the analysis. Among these patients, 103 (30.45%) died, giving a crude death rate of 25.53 per 1000 (95% CI: 21.05–30.98) person-days of follow-up. The overall median survival time was 44 days. The independent predictors of mortality after diagnosis of traumatic brain injury were admission Glasgow coma scale score ≤ 8 (adjusted hazard ratio (AHR): 4.85; 95% confidence interval (CI): 1.73–13.62), bilateral non-reactive pupils at admission (AHR: 2.00 (95% CI: 1.10–3.71), elevated systolic blood pressure at admission (AHR: 0.31; 95% CI:0.11–0.86), elevated diastolic blood pressure at admission (AHR: 3.54; 95% CI: 1.33–9.43), and haematoma evacuation (AHR: 0.42; 95% CI: 0.16–0.90). Discussion: The Survival status of traumatic brain injury patients was relatively low in this study. Glasgow coma scale score, bilateral non-reactive pupils, and elevated blood pressure were significant predictors of mortality. Further prospective follow-up studies that include residence and occupation are recommended.