Background: Premarital sexual practice becomes a common phenomenon among youths in Ethiopia. It is usually associated with unwanted pregnancies, abortions, and sexually transmitted diseases including HIV/AIDS. Objective: This study is aimed at assessing the magnitude and determinants of premarital sexual practice among Ethiopian youths. Methods: A community-based cross-sectional study was conducted in all regions of Ethiopia from January 18 to June 27, 2016. A total of 7389 youths with the age range from 19 to 24 were included in the present study. Bivariable and multivariable binary logistic regression analyses were employed to identify factors associated with premarital sex. A 95% CI and p value < 0.05 were used to declare statistical significance. Result: The prevalence of premarital sexual practice was 10.8% (95% CI, 10%-11.5%). Being in the age group of 20-24 (AOR = 3.6, 95% CI (2.8, 4.6)), male sex (AOR = 1.7, 95% CI (1.3, 2.2)), employed (AOR = 1.4, 95% CI (1.03, 1.8)), from pastoral region (AOR = 1.4, 95% CI (1.3,2.4)), having mobile phone (AOR = 1.7, 95% CI, (1.3, 2.3)), ever use of internet (AOR = 1.8, 95% CI (1.3, 2.5)), ever drinking alcohol (AOR = 2.4, 95% CI (1.7, 2.5)), ever chewed khat (AOR = 2.4, 95% CI (1.6, 3.5), and ever tested for HIV (AOR = 1.3, 95% CI (1.1,1.6)) were statistically significant factors associated with premarital sex. Conclusion: For every 10 youths, at least one of them had sexual intercourse before they got married. Being in the age group of 20-24, male sex, employed, from a pastoral region, having a mobile phone, ever use of the internet, alcohol drinking, khat chewing, and ever tested for HIV were important factors affecting premarital sex. Thus, national sexual education and reproductive health behavior change interventions should give due attention to those groups. Furthermore, adequate education should be given about premarital sexual intercourse when youths come for HIV tests.