Background Coronavirus disease 2019 (COVID-19) is a highly contagious viral infection, and it has negative effects on public health. The practice of preventive measures of the disease supports containment processes of the spread of coronavirus. However, the practice of preventive measures is affected by several associated risk factors. Objective This study aimed to investigate the associated factors that limit the youths' practice of preventive measures against COVID-19 in the study area. Methods A community-based cross-sectional study was conducted. The study used a quantitative approach for collecting data from 384 youths using a survey method. Not practicing preventive measures was measured to determine whether or not youths applied hygiene practices, kept their distance, restricted their movements, and sought self-help or support in the past two months. Descriptive statistics were used to assess the distribution of study participants, and a binary regression model was executed to examine the association factors with inability to practice preventive measures with a p-value Results Male youths (Adjusted Odds Ratio (AOR) = 0.06; 95% CI: 0.02, 0.16) were less likely to practice preventive measures. Older youth (AOR = 1.33; 95% CI: 1.13, 1.56), with higher education level (AOR = 1.03; 95% CI: 1.01, 1.06), and who had higher income (AOR = 1.34; 95% CI: 1.02, 1.78) were more likely to practice preventive measures. Further, the belief in the body's immunity to resist the disease (AOR = 0.27; 95% CI: 0.11, 0.67), lack of paying attention to the disease (AOR = 0.07; 95% CI: 0.01, 0.73), ignorance of evidence to the disease (AOR = 0.31; 95% CI: 0.13, 0.74), ease of restriction of movements (AOR = 0.29; 95% CI: 0.12, 0.72), lack of sensitization to actions in the community (AOR = 0.39; 95% CI: 0.16, 0.96), and substance use (AOR = 0.11; 95% CI: 0.05, 0.21) were other factors that were inversely related to practicing preventive measures. Conclusions The findings suggested that more intervention efforts, by either communicating to or reaching out all groups, should be employed. All segments of the population should be equipped with the facts that effectively support them practice preventive measures against the disease. Finally, the results suggested that youths should abstain from substance use, keep their distance in their pastime and avoid crowdings.