his study examined coronavirus disease 2019 (COVID-19) prevention knowledge among community residents in Eastern Ethiopia to support public health interventions and vaccination coverage. A cross-sectional survey in August-September 2021 recruited 880 participants from households in a Health and Demographic Surveillance System (HDSS) in Harari and Oromia, Ethiopia. Participants were randomly selected and interviewed in person using tablets and a standardized questionnaire. Principal components analysis was used to create a score representing COVID-19 prevention knowledge. Quasi-Poisson regression was used to examine associations between demographic characteristics and COVID-19 prevention knowledge. The survey also assessed awareness of community/government COVID-19 prevention measures and healthcare services for under-5 children and pregnant women. The most cited COVID-19 prevention measures were handwashing with soap (91.5%) and wearing facemasks (89.2%); least mentioned were avoiding travel (22.2%) and wearing medical gloves (20.3%). Commonly recognized community/government measures included school closures (77.0%), avoiding gatherings (75.2%), and staying home (62.3%). Adjusted analyses demonstrated higher COVID-19 prevention knowledge among rural participants, those aged ≥65 years (reference: <25), with secondary education (reference: no education), with monthly income of ≥2,001 Birr (reference: 0–1,200), and were farmers, domestic/subsistence workers, or government employees (reference: unemployed). Knowledge was lower among households with ≥5 household members. Of households with under-5 children and pregnant women, 9.4% and 12.3% missed medical care visits since mid-March 2020 consequent to the pandemic. Public health interventions to reduce COVID-19 transmission rely on risk perception and knowledge. Understanding these factors can help Ethiopian authorities design effective health education programs to control community and household SARS-CoV-2 transmission.