To meet the educational, physical, social, and emotional needs of children, many U.S. schools opened for in-person learning during fall 2020 by implementing strategies to prevent transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). To date, there have been no U.S. studies comparing COVID-19 incidence in schools that varied in implementing recommended prevention strategies, including mask requirements and ventilation improvements* (2). Using data from Georgia kindergarten through grade 5 (K-5) schools that opened for in-person learning during fall 2020, CDC and the Georgia Department of Public Health (GDPH) assessed the impact of school-level prevention strategies on incidence of COVID-19 among students and staff members before the availability of COVID-19 vaccines.† Among 169 K-5 schools that participated in a survey on prevention strategies and reported COVID-19 cases during November 16-December 11, 2020, COVID-19 incidence was 3.08 cases among students and staff members per 500 enrolled students.§ Adjusting for county-level incidence, COVID-19 incidence was 37% lower in schools that required teachers and staff members to use masks, and 39% lower in schools that improved ventilation, compared with schools that did not use these prevention strategies. Ventilation strategies associated with lower school incidence included methods to dilute airborne particles alone by opening windows, opening doors, or using fans (35% lower incidence), or in combination with methods to filter airborne particles with high-efficiency particulate absorbing (HEPA) filtration with or without purification with ultraviolet germicidal irradiation (UVGI) (48% lower incidence). Multiple strategies should be implemented to prevent transmission of SARS-CoV-2 in schools (2); mask requirements for teachers and staff members and improved ventilation are important strategies that elementary schools could implement as part of a multicomponent approach to provide safer, in-person learning environments. Universal and correct mask use is still recommended by CDC for adults and children in schools regardless of vaccination status (2).