Chronic diseases such as heart disease, cancer, and diabetes are leading drivers of mortality worldwide, underscoring the need for improved efforts around early detection and prediction. The pathophysiology and management of chronic diseases have benefitted from emerging fields in molecular biology like genomics, transcriptomics, proteomics, glycomics, and lipidomics. The complex biomarker and mechanistic data from these “omics” studies present analytical and interpretive challenges, especially for traditional statistical methods. Machine learning (ML) techniques offer considerable promise in unlocking new pathways for data‐driven chronic disease risk assessment and prognosis. This review provides a comprehensive overview of state‐of‐the‐art applications of ML algorithms for chronic disease detection and prediction across datasets, including medical imaging, genomics, wearables, and electronic health records. Specifically, we review and synthesize key studies leveraging major ML approaches ranging from traditional techniques such as logistic regression and random forests to modern deep learning neural network architectures. We consolidate existing literature to date around ML for chronic disease prediction to synthesize major trends and trajectories that may inform both future research and clinical translation efforts in this growing field. While highlighting the critical innovations and successes emerging in this space, we identify the key challenges and limitations that remain to be addressed. Finally, we discuss pathways forward toward scalable, equitable, and clinically implementable ML solutions for transforming chronic disease screening and prevention.