What is already known about this topic? Many kindergarten through grade 12 (K-12) schools have implemented strategies to limit school-associated SARS-CoV-2 transmission. What is added by this report? In 22 participating K-12 schools implementing multiple COVID-19 mitigation strategies, school-based SARS-CoV-2 secondary transmission was detected in two of 102 tested close contacts of 37 persons with COVID-19. Among 21 tested student contacts participating in a modified quarantine, all SARS-CoV-2 test results were negative. What are the implications for public health practice? Schools implementing strategies including mask mandates, physical distancing, and increased ventilation had much lower SARS-CoV-2 transmission than in the community. K-12 schools should continue implementing these measures and following CDC isolation and quarantine guidance to minimize secondary transmission in schools.