Background: Into the third year of the COVID-19 pandemic and the second year of in-person learning for many K-12 schools in the United States, the benefits of mitigation strategies in this setting are still unclear. We compare COVID-19 cases in school-aged children and adolescents between a school district with a mandatory mask-wearing policy to one with an optional mask-wearing policy, during and after the peak period of the Delta variant wave of infection. Methods: COVID-19 cases during the Delta variant wave (August 2021) and post the wave (October 2021) were obtained from public health records. Cases of K-12 students, stratified by grade level (elementary, middle, and high school) and school districts across two counties, were included in the statistical and spatial analyses. COVID-19 case rates were determined and spatially mapped. Regression was performed adjusting for specific covariates. Results: Mask-wearing was associated with lower COVID-19 cases during the peak Delta variant period; overall, regardless of the Delta variant period, higher COVID-19 rates were seen in older aged students. Conclusion: This study highlights the need for more layered prevention strategies and policies that take into consideration local community transmission levels, age of students, and vaccination coverage to ensure that students remain safe at school while optimizing their learning environment.