Increasing the availability of safe blood is a major challenge in developing countries. Given the scant amount of community-based data in Africa, this study examines the knowledge, attitudes, and practices of blood donation of Ethiopian adults.A cross-sectional study was conducted on 421 adult residents of Adama town using face-to-face interviews with translated questionnaires. Knowledge and attitude levels were assessed using a set of questions and those who answered above mean for knowledge and attitude questions were categorized as above-average knowledge level and favorable attitude, respectively. The data were coded and entered into EPI Info™ version 7, transferred to SPSS version 25 for cleaning and analysis. All variables with p<0.25 in the bivariable analysis were examined as candidate variables in the multivariable logistic regression models.Less than half, 47% (95% CI: 42-52%) of the study participants have above-average knowledge level about blood donation and 48% (95% CI: 43-53%) have favorable attitudes towards blood donation. Only 17% (95% CI: 13-21%) of study participants ever donated blood of which 14.6% of them donated for replacement and less than 2% (1.95%) are voluntary donors. Younger age of 18-25 AOR: 95% CI: 3.40 (1.30, 12.43), having good knowledge AOR: 95% CI: 2.21 (1.26, 3.89) and favorable attitude AOR: 95% CI: 10.25 (4.90, 21.44) were factors independently associated with blood donation practice.The level of blood donation practiced in the study area is low. Low knowledge and poor attitudes are independent predictors of low inclination to donate, so awareness creation and improving attitudes in blood donation campaigns, particularly among older people is necessary to increase voluntary blood donation.