Notable increases in youth mental health problems combined with strains on the already stretched mental health workforce raise concerns that there will be an ensuing increase in youth suicide thoughts, behaviors, and even deaths. Schools are recognized as crucial settings for youth mental health support and suicide prevention activities, yet schools also face staff shortages and ever-increasing responsibilities for student well-being. Evidence is emerging that prevention programs originally designed to improve problem-solving skills and social-emotional functioning in youth have demonstrated downstream, “crossover effects,” that is, unanticipated benefits, on youth suicidal behavior. Relatively little research on crossover effects has been conducted within school settings, despite the strong potential for commonly administered programs to have an impact on later suicide risk. We review key suicide risk factors and their proposed mechanisms of action; we also discuss factors that may protect against suicide risk. We then identify upstream prevention programs targeting the same factors and mechanisms; these programs may hold promise for downstream, crossover effects on youth suicide risk. This paper is intended to provide a framework to help researchers, practitioners, and policymakers as they consider how to prevent youth suicide using existing school-based resources. Rigorous investigation of upstream prevention programs is urgently needed to determine ideal approaches schools and communities can deploy to prevent youth suicide.