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Background Prognostic indices can enhance personalized predictions of health burdens. However, a simple, practical, and reproducible tool is lacking for clinical use. This study aimed to develop a machine learning-based prognostic index for predicting all-cause mortality in community-dwelling older individuals. Methods We utilized the Healthy Aging Longitudinal Study in Taiwan (HALST) cohort, encompassing data from 5 663 participants. Over the 5-year follow-up, 447 deaths were confirmed. A machine learning-based routine blood examination prognostic index (MARBE-PI) was developed using common laboratory tests based on machine learning techniques. Participants were grouped into multiple risk categories by stratum-specific likelihood ratio analysis based on their MARBE-PI scores. The MARBE-PI was subsequently externally validated with an independent population-based cohort from Japan. Results Beyond age, sex, education level, and BMI, 6 laboratory tests (low-density lipoprotein, albumin, aspartate aminotransferase, lymphocyte count, high-sensitivity C-reactive protein, and creatinine) emerged as pivotal predictors via stepwise logistic regression (LR) for 5-year mortality. The area under curves of MARBE-PI constructed by LR were 0.799 (95% confidence interval [95% CI]: 0.778–0.819) and 0.756 (95% CI: 0.694–0.814) for the internal and external validation data sets, and were 0.801 (95% CI: 0.790–0.811) and 0.809 (95% CI: 0.774–0.845) for the extended 10-year mortality in both data sets, respectively. Risk categories stratified by MARBE-PI showed a consistent dose–response association with mortality. The MARBE-PI also performed comparably with indices constructed with clinical health deficits and/or laboratory results. Conclusions The MARBE-PI is considered the most applicable measure for risk stratification in busy clinical settings. It holds potential to pinpoint older individuals at elevated mortality risk, thereby aiding clinical decision-making. [ABSTRACT FROM AUTHOR]