Traumatic brain injury (TBI) is the major cause of mortality and morbidity in severely-injured patients worldwide. This retrospective nationwide study aimed to evaluate the age- and severity-related in-hospital mortality trends and mortality risks of patients with severe TBI from 2009 to 2018 to establish effective injury prevention measures. We retrieved information from the Japan Trauma Data Bank dataset between 2009 and 2018. The inclusion criteria for this study were patients with severe TBI defined as those with an Injury Severity Score ≥ 16 and TBI. In total, 31,953 patients with severe TBI (32.6%) were included. There were significant age-related differences in characteristics, mortality trend, and mortality risk in patients with severe TBI. The in-hospital mortality trend of all patients with severe TBI significantly decreased but did not improve for patients aged ≤ 5 years and with a Glasgow Coma Scale (GCS) score between 3 and 8. Severe TBI, age ≥ 65 years, fall from height, GCS score 3–8, and urgent blood transfusion need were associated with a higher mortality risk, and mortality risk did not decrease after 2013. Physicians should consider specific strategies when treating patients with any of these risk factors to reduce severe TBI mortality.