This study aimed to identify barriers and facilitators to comprehensive, school-based physical activity (PA) promotion among adolescents prior to and during the coronavirus disease of 2019 (COVID-19) pandemic, considering the perspectives of students, parents, and school staff. Data were collected from 2020 to 2021 using semi-structured individual interviews with students (n = 15), parents (n = 20), and school staff (n = 8) at a Title I middle school (i.e. high percentage of students from low-income families). Two theoretical frameworks guided analysis: the Comprehensive School Physical Activity Program framework and Bronfenbrenner’s ecological systems theory. Using an iteratively developed codebook, data were coded, thematically analyzed, and synthesized. PA barriers and facilitators were present throughout the school day, at home, and in the community. Key determinants included pandemic-induced challenges (e.g. COVID-19 exposure); neighborhood characteristics/weather (e.g. neighborhood safety); school–family communication/collaboration; implementation climate (i.e. school staff’s support for programming); time, spatial, and monetary resources (e.g. funding); staffing capacity/continuity and school champions; staffing creativity and adaptability; PA opportunities before, during, and after school; and child’s motivation/engagement. Efforts to improve school-based PA programs, irrespective of pandemic conditions, should include strategies that address factors at the community, school, family and individual levels. School–family communication/collaboration, school staff programming support, and PA opportunities throughout the day can help promote comprehensive, school-based PA.