This umbrella review evaluates the existing meta-analytic evidence linking exposure to ultra-processed foods, as defined by the Nova food classification system, to adverse health outcomes. The review includes 45 unique pooled analyses from cohort, case-control, and cross-sectional studies, involving a total of 9888,373 participants. Overall, direct associations were found between exposure to ultra-processed foods and 32 health parameters, including mortality, cancer, mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Convincing evidence (class I) supported higher risks of incident cardiovascular disease-related mortality and type 2 diabetes, as well as higher risks of prevalent anxiety and common mental disorder outcomes. Highly suggestive evidence (class II) indicated higher risks of all-cause mortality, heart disease-related mortality, type 2 diabetes, depressive outcomes, adverse sleep-related outcomes, wheezing, and obesity. The review also assessed the quality of evidence using the GRADE framework, with 22 pooled analyses rated as low quality, 19 as very low, and four as moderate. The findings suggest that greater exposure to ultra-processed foods is associated with a higher risk of adverse health outcomes, particularly in cardiometabolic, mental health, and mortality outcomes. These findings support the need for urgent mechanistic research and public health actions to reduce dietary exposure to ultra-processed foods.This umbrella review evaluates the existing meta-analytic evidence linking exposure to ultra-processed foods, as defined by the Nova food classification system, to adverse health outcomes. The review includes 45 unique pooled analyses from cohort, case-control, and cross-sectional studies, involving a total of 9888,373 participants. Overall, direct associations were found between exposure to ultra-processed foods and 32 health parameters, including mortality, cancer, mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Convincing evidence (class I) supported higher risks of incident cardiovascular disease-related mortality and type 2 diabetes, as well as higher risks of prevalent anxiety and common mental disorder outcomes. Highly suggestive evidence (class II) indicated higher risks of all-cause mortality, heart disease-related mortality, type 2 diabetes, depressive outcomes, adverse sleep-related outcomes, wheezing, and obesity. The review also assessed the quality of evidence using the GRADE framework, with 22 pooled analyses rated as low quality, 19 as very low, and four as moderate. The findings suggest that greater exposure to ultra-processed foods is associated with a higher risk of adverse health outcomes, particularly in cardiometabolic, mental health, and mortality outcomes. These findings support the need for urgent mechanistic research and public health actions to reduce dietary exposure to ultra-processed foods.