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In the United States, schools closed in March 2020 due to COVID-19 and began reopening in August 2020, despite continuing transmission of SARS-CoV-2. In states where in-person instruction resumed at that time, two major unknowns were the capacity at which schools would operate, which depended on the proportion of families opting for remote instruction, and adherence to face-mask requirements in schools, which depended on cooperation from students and enforcement by schools. To determine the impact of these conditions on the statewide burden of COVID-19 in Indiana, we used an agent-based model calibrated to and validated against multiple data types. Using this model, we quantified the burden of COVID-19 on K-12 students, teachers, their families, and the general population under alternative scenarios spanning three levels of school operating capacity (50 %, 75 %, and 100 %) and three levels of face-mask adherence in schools (50 %, 75 %, and 100 %). Under a scenario in which schools operated remotely, we projected 45,579 (95 % CrI: 14,109–132,546) infections and 790 (95 % CrI: 176–1680) deaths statewide between August 24 and December 31. Reopening at 100 % capacity with 50 % face-mask adherence in schools resulted in a proportional increase of 42.9 (95 % CrI: 41.3–44.3) and 9.2 (95 % CrI: 8.9–9.5) times that number of infections and deaths, respectively. In contrast, our results showed that at 50 % capacity with 100 % face-mask adherence, the number of infections and deaths were 22 % (95 % CrI: 16 %–28 %) and 11 % (95 % CrI: 5 %–18 %) higher than the scenario in which schools operated remotely. Within this range of possibilities, we found that high levels of school operating capacity (80–95 %) and intermediate levels of face-mask adherence (40–70 %) resulted in model behavior most consistent with observed data. Together, these results underscore the importance of precautions taken in schools for the benefit of their communities.