Although children living in low- and middle-income countries (LMICs) account for 90% of the global population of children, depression, and anxiety among children in LMICs have 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. We conducted a large-scale epidemiological study of depression and anxiety among 53,421 elementary and junior high school-aged children across China. 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 a higher risk for both depression and anxiety symptoms, while socioeconomic status has varying associations to depression and anxiety symptoms. Our results also show consistent correlations between depression and anxiety symptoms and standard math test scores. These findings underscore the importance of identification, prevention, and treatment of youth depression and anxiety 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.