© 2017 Academic Pediatric Association Objective Chronic physical health conditions are highly prevalent in youth, frequently persisting into adulthood and contributing to the current and future health care burden in the United States. Our study evaluated associations of chronic physical health conditions with depressive and physiological anxiety symptoms in a community sample of youth and examined how those associations changed from early to midadolescence. Methods In this longitudinal study of 5147 youth, students and their caregivers were interviewed when youth were in grades 5 (mean age = 11), 7 (mean age = 13), and 10 (mean age = 16). Caregivers reported family sociodemographics, youth race/ethnicity, and youth chronic physical health history at baseline. Youth reported their depressive symptoms at each time point and their physiological anxiety symptoms at grades 7 and 10. Results At age 11, 28.5% had experienced a chronic physical health condition. Having any chronic physical health condition was related to elevated depressive symptoms at age 11 (2.05 ± 0.05 vs 1.89 ± 0.03; mean ± standard error; P <.01) and anxiety symptoms at age 16 (2.72 ± 0.06 vs 2.55 ± 0.04; P <.05). Experiencing multiple conditions was also related to experiencing more depressive symptoms (b = 0.13; P <.01) and physiological anxiety symptoms (b = 0.13; P <.05). After adjusting for previous mental health symptoms, having any condition still predicted anxiety at age 16. Conclusions Children with chronic physical health conditions have an increased risk of depressive symptoms and physiological anxiety symptoms, especially in early and midadolescence. Repeated screening for these symptoms may help identify children in need of interventions.