Background Sepsis is a life-threatening state resulting from an ineffective biological host response to infection resulting in organ dysfunction with high mortality, especially in intensive care unit (ICU) settings. Despite progress in its management, early prognosis of sepsis remains difficult. Severity scoring systems have been developed to assess disease severity and predict outcomes, including the Sequential Organ Failure Assessment (SOFA) score and the Simplified Acute Physiology Score-3 (SAPS-3). This study sought to evaluate and compare the prognostic utility of SOFA and SAPS-3 scores in predicting ICU mortality in patients with sepsis at a tertiary care center in South India. Methods A prospective observational study was performed on 316 adult patients who were admitted to the medical intensive care unit with a confirmed or probable diagnosis of sepsis based on the criteria of Sepsis-3 definition. SOFA and SAPS-3 scores were determined using the relevant worst clinical and laboratory parameters recorded within the first 24 hours of ICU admission. Follow-up continued through discharge or death. Statistical analysis included chi-square tests, binomial logistic regression for predictor variables, and Receiver Operating Characteristic (ROC) curve to ascertain the predictive accuracy of each scoring system. Results Of the 316 sepsis patients enrolled, ICU mortality was 56%, with non-survivors being significantly older and having higher rates of ventilation and inotrope use (p Conclusion The prognostic value of SOFA and SAPS-3 scores for predicting ICU mortality among patients with sepsis was excellent. SOFA also had slightly more discriminative ability than SAPS-3, making it a useful and trusted tool for predicting outcomes early and guiding clinical decisions in critical care.