This umbrella review of epidemiological meta-analyses examines the association between exposure to ultra-processed foods (as defined by the Nova classification system) and adverse health outcomes. Systematic searches of MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, along with manual searches of reference lists from 2009 to June 2023, identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations, involving 9,888,373 participants. Overall, direct associations were found between ultra-processed food exposure and 32 (71%) health parameters, including mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Convincing evidence (class I) was found for associations with cardiovascular disease mortality, type 2 diabetes, and common mental disorders. Highly suggestive evidence (class II) was found for all-cause mortality, heart disease mortality, type 2 diabetes, and depressive outcomes. The GRADE framework categorized the quality of evidence as high, moderate, low, or very low. The review found that greater exposure to ultra-processed foods was associated with higher risks of cardiovascular disease mortality, type 2 diabetes, anxiety, and common mental disorders. The findings support the need for further mechanistic research and public health actions to reduce ultra-processed food consumption. The study highlights the importance of addressing ultra-processed food exposure to improve population health. The review is the first comprehensive synthesis of current evidence from meta-analyses of epidemiological studies, exploring the associations between dietary exposure to ultra-processed foods and various adverse health outcomes. The study used rigorous systematic methods, including duplicate study selection and data extraction, alongside evidence classification criteria and GRADE assessments, to evaluate the credibility and quality of the pooled analyses. The review found that ultra-processed foods are associated with a higher risk of adverse health outcomes, particularly cardiometabolic, common mental disorder, and mortality outcomes. The findings provide a rationale for developing and evaluating population-based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. The study also informs and supports urgent mechanistic research.This umbrella review of epidemiological meta-analyses examines the association between exposure to ultra-processed foods (as defined by the Nova classification system) and adverse health outcomes. Systematic searches of MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, along with manual searches of reference lists from 2009 to June 2023, identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations, involving 9,888,373 participants. Overall, direct associations were found between ultra-processed food exposure and 32 (71%) health parameters, including mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Convincing evidence (class I) was found for associations with cardiovascular disease mortality, type 2 diabetes, and common mental disorders. Highly suggestive evidence (class II) was found for all-cause mortality, heart disease mortality, type 2 diabetes, and depressive outcomes. The GRADE framework categorized the quality of evidence as high, moderate, low, or very low. The review found that greater exposure to ultra-processed foods was associated with higher risks of cardiovascular disease mortality, type 2 diabetes, anxiety, and common mental disorders. The findings support the need for further mechanistic research and public health actions to reduce ultra-processed food consumption. The study highlights the importance of addressing ultra-processed food exposure to improve population health. The review is the first comprehensive synthesis of current evidence from meta-analyses of epidemiological studies, exploring the associations between dietary exposure to ultra-processed foods and various adverse health outcomes. The study used rigorous systematic methods, including duplicate study selection and data extraction, alongside evidence classification criteria and GRADE assessments, to evaluate the credibility and quality of the pooled analyses. The review found that ultra-processed foods are associated with a higher risk of adverse health outcomes, particularly cardiometabolic, common mental disorder, and mortality outcomes. The findings provide a rationale for developing and evaluating population-based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. The study also informs and supports urgent mechanistic research.