During fall 2020, many U.S. kindergarten through grade 12 (K-12) schools closed campuses and instituted remote learning to limit in-school transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). A New Jersey grade 9-12 boarding school with 520 full-time resident students, 255 commuter students, and 405 faculty and staff members implemented a comprehensive mitigation strategy that included universal masking, testing, upgraded air-handling equipment to improve ventilation, physical distancing of ≥6 ft, contact tracing, and quarantine and isolation protocols to prevent and control transmission of SARS-CoV-2 among students, faculty, and staff members. Mandatory twice-weekly screening using real-time reverse transcription-polymerase chain reaction (RT-PCR) testing of all students and staff members during August 20-November 27, 2020, resulted in the testing of 21,449 specimens. A total of 19 (5%) of 405 faculty and staff members and eight (1%) of 775 students received positive test results; only two identified cases were plausibly caused by secondary transmission on campus. Comprehensive mitigation approaches including frequent testing and universal masking can help prevent outbreaks in in-person high school settings even when community transmission is ongoing.