Chronic kidney disease (CKD) remains one of the most prominent global causes of mortality worldwide, necessitating accurate prediction models for early detection and prevention. In recent years, machine learning (ML) techniques have exhibited promising outcomes across various medical applications. This study introduces a novel ML-driven monogram approach for early identification of individuals at risk for developing CKD stages 3–5. This retrospective study employed a comprehensive dataset comprised of clinical and laboratory variables from a large cohort of diagnosed CKD patients. Advanced ML algorithms, including feature selection and regression models, were applied to build a predictive model. Among 467 participants, 11.56% developed CKD stages 3–5 over a 9-year follow-up. Several factors, such as age, gender, medical history, and laboratory results, independently exhibited significant associations with CKD (p < 0.05) and were utilized to create a risk function. The Linear regression (LR)-based model achieved an impressive R-score (coefficient of determination) of 0.954079, while the support vector machine (SVM) achieved a slightly lower value. An LR-based monogram was developed to facilitate the process of risk identification and management. The ML-driven nomogram demonstrated superior performance when compared to traditional prediction models, showcasing its potential as a valuable clinical tool for the early detection and prevention of CKD. Further studies should focus on refining the model and validating its performance in diverse populations.