The coronavirus disease 2019 (COVID-19) pandemic has disrupted in-person learning in the United States, with approximately one half of all students receiving online-only instruction since March 2020.* Discontinuation of in-person schooling can result in many hardships (1) and disproportionately affects families of lower socioeconomic status (2). Current evidence suggests that transmission of SARS-CoV-2, the virus that causes COVID-19, in kindergarten through grade 12 (K-12) schools might not significantly contribute to COVID-19 spread nationwide (3). During August 31-November 29, 2020, COVID-19 cases, spread, and compliance with mask use were investigated among 4,876 students and 654 staff members who participated in in-person learning in 17 K-12 schools in rural Wisconsin. School-attributable COVID-19 case rates were compared with rates in the surrounding community. School administration and public health officials provided information on COVID-19 cases within schools. During the study period, widespread community transmission was observed, with 7%-40% of COVID-19 tests having positive results. Masking was required for all students and staff members at all schools, and rate of reported student mask-wearing was high (>92%). COVID-19 case rates among students and staff members were lower (191 cases among 5,530 persons, or 3,453 cases per 100,000) than were those in the county overall (5,466 per 100,000). Among the 191 cases identified in students and staff members, one in 20 cases among students was linked to in-school transmission; no infections among staff members were found to have been acquired at school. These findings suggest that, with proper mitigation strategies, K-12 schools might be capable of opening for in-person learning with minimal in-school transmission of SARS-CoV-2.