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Background: Although children living in low-and middle-income countries (LMICs) account for 90% of the global population of children, mental health among children in LMICs has been understudied. This study examines the prevalence of depression and anxiety and their associations with biological and psychosocial factors among children across China, with a focus on rural areas. Methods: We conduct a large-scale epidemiological study among 53,421 elementary and junior high school-aged children across China’s rural areas. Findings: The results show that 20% are at risk for depression, 6% are at risk for generalized anxiety, and 68% are at risk for at least one type of anxiety. Girls and junior high school students show higher risk for mental health problems; socioeconomic status has varying associations to mental health. Our results also show robust correlations between mental health and cognition. Interpretation: These findings underscore the importance of identification, prevention, and treatment of youth mental health problems in underdeveloped areas. As China constitutes 15% of the global population of children under age 18, this study offers valuable information to the field of Global Mental Health, especially given its findings of high prevalence for multiple mental health problems and robust correlations between mental health and cognition. Funding Statement: This work was supported by the Enlight Foundation. Declaration of Interests: The authors have no conflicts of interest. Ethics Approval Statement: The six surveys conducted by the authors and their colleagues were approved by the Stanford University Institutional Review Board. Study permissions were also obtained from the Chinese government. In accordance with IRB requirements, all children involved in the surveys provided oral assent for the project, and the school principals – who serve as the children’s legal guardians while they are in school—also provided their written consent.