Background: Diffuse axonal injury (DAI) is a key determinant of prognosis in traumatic brain injury (TBI), yet the interaction between DAI severity and associated hemorrhagic lesions is not well defined, especially in low- and middle-income countries (LMICs). Methods: We conducted a retrospective cohort study of 283 adults with moderate-to-severe TBI admitted to a tertiary hospital in Ecuador (2019–2023). DAI severity was graded anatomically using CT or MRI, and patients were stratified by the presence of hemorrhagic lesions. Demographic, clinical, metabolic, and radiological variables were collected. Outcomes were evaluated at 6 months with the Glasgow Outcome Scale–Extended (GOS-E). Logistic and ordinal regression models identified predictors of mortality and disability. Results: Of 283 patients, 141 had isolated DAI and 142 had DAI with hemorrhage. Baseline demographics were similar. Patients with hemorrhagic lesions had lower median Glasgow Coma Scale scores (6 vs 9, p < 0.001), more frequent hyperglycemia (15.5 % vs 7.1 %, p = 0.045), and greater surgical needs (77.5 % vs 16.3 %, p < 0.001). Complications, including pneumonia and central nervous system infections, were more frequent in the hemorrhagic group (63.9 % vs 45.7 %, p < 0.001). At 6 months, functional outcomes were significantly worse with hemorrhage (median GOS-E 7 vs 8, p < 0.001). Multivariable regression identified Grade III DAI as the strongest predictor of mortality (OR 20.02, 95 % CI 7.99–50.15) and disability (OR 71.59, 95 % CI 23.11–221.77). Hemorrhagic lesions predicted poor functional recovery (OR 2.08, 95 % CI 1.24–3.48) but not mortality. Conclusions: DAI grading is the most powerful prognostic factor in severe TBI, while hemorrhagic lesions primarily worsen disability. In LMICs, CT-based assessment remains essential for prognostic stratification and guiding rehabilitation strategies.