The youth mental health crisis has become so acute during the COVID-19 pandemic that a coalition of U.S. pediatric health experts has declared it a national emergency1. To which extent this crisis can be attributed to the pandemic or the different pandemic measures is unknown. School closures are among the most heavily debated pandemic measures, with insufficient evidence on their costs2,3,4,5. We seek to narrow this blind spot, by compiling data on the manifold school closure and re-opening strategies implemented across the federal states of Germany at the onset of the pandemic and combining it with data from a nationwide, population-based, longitudinal survey on youth mental health and the largest crisis helpline for children and adolescents. We show that prolonged school closures led to a significant deterioration in youth health-related quality of life, precipitating first signs of mental health problems. Effects were most severe among boys, less mature adolescents, and families with limited living space. Young people also increasingly sought support from crisis helplines to discuss arising family and friendship problems. Importantly, the effects persist even when abstracting from the overall strain imposed by the pandemic or further pandemic measures. Indeed, school closures explain around two thirds of the aggravation of the youth mental health crisis throughout the first pandemic wave and there is no sign for a swift recovery.