During the COVID-19 pandemic, the youth mental health crisis has reached unprecedented levels. To which extent school closures, one of the most heavily debated pandemic measures, have contributed to or even caused this crisis is largely unknown. We seek to narrow this blind spot, by combining quasi-experimental variation in school closure and reopening strategies across the German federal states at the onset of the pandemic with nationwide, population-based survey data on youth mental health and high-frequency data from the largest crisis helpline. We show that prolonged school closures led to a substantial deterioration in youth health-related quality of life, precipitating early signs of mental health problems. The effects were most severe among boys, younger adolescents, and families with limited living space. We further provide evidence that family problems are a major issue that adolescents were struggling with when denied access to school. Overall, school closures largely explain the deterioration of youth mental health over the first pandemic wave.