Objective: Despite growing awareness of the high prevalence of adverse childhood experiences (ACEs) in community samples of adolescents, little work has examined the impact of ACEs on adolescence and well-being during this critical period of development. Much research has focused on retrospective reports of ACEs by adults and adult physical and mental health, finding that ACEs contribute to a range of diseases and mental health disorders in adulthood. This study examined differences in self-reported mental health, nonsuicidal self-injury, suicidality, violence, and substance use between adolescents without self-reported history of ACEs, youth with one self-reported ACE, and youth with self-reported multiple (2 or more) ACEs. Method: The sample included 1,532 adolescents who completed the Youth Risk Behavior Surveillance Survey in their local high schools. By local consensus, this national survey was augmented with questions exploring prevalence of 11 commonly identified ACEs. Results: After controlling for age, gender, and race, youth with multiple ACEs reported 3 to 15 times the odds of a range of negative health experiences. Conclusions: Findings indicate a serious burden of ACEs on adolescent social emotional well-being. This study did not include youth in out of school placements or who were not present the day the survey was given, and thus represent youth who may benefit from universal prevention and intervention programs. Universal screening of ACEs and health-related outcomes suggests that reporting multiple ACEs is strongly related to a wide range of mental health, violence, and substance use histories. Clinical Impact Statement Youth with multiple ACEs report significantly greater likelihood of mental health problems, suicidality, substance use, and aggression than youth without ACEs. The largest differences between youth with multiple ACEs and youth without ACEs were found in suicidality (i.e., suicide attempts, suicidal ideation) and violence (e.g., weapon and gun possession). Suicide and violence prevention should therefore be a key part of trauma interventions. Youth with self-reported exposure to traumatic events should be screened for mental health, suicidality, substance use, and violence risk; similarly, youth demonstrating high risk behaviors should be screened for trauma. Integrated treatments for mental health, substance use, and aggression for youth survivors of trauma are indicated. Because a third of youth reported multiple ACEs and having multiple ACEs were associated with a broad range of high risk mental health, substance use, and violence indicators, a comprehensive system of care that is trauma and culturally responsive to the needs of youth and their families is indicated.