Background: Novel coronavirus-2019 (COVID-19) is a highly infectious disease that has caused a global pandemic. As of April, 2020, there were 74 confirmed cases of COVID-19 in Ethiopia, but none in Debre Berhan where this study was conducted. Under these conditions we sought to assess what undergraduate students at Debre Berhan University knew about COVID-19and how it shaped their attitudes and practices regarding this disease. Methods: A cross-sectional survey was conducted from March 18–24, 2020 among undergraduate students at Debre Berhan University. The data were checked for completeness, coded, entered into Epi Data VS 3.1, and then exported into STATA™ Version 14 software for analysis. Descriptive statistics were used to describe the relationship between study participants and the relevant variables. Binary logistic regression analyses were used to identify factors. Factors were selected with a backward stepwise method. Adjusted odds ratios (AORs) and their 95% confidence intervals (CIs) were used to assess the associations between variables and knowledge, attitude and practices (KAP). Variables with a p value ≤ 0.05 following multivariable analysis were considered significant.Results: A total of 546 participants were included in this study with a mean age of 21.74 years old. In this study, approximately 73.8% of the study participants were knowledgeable about COVID-19 and their overall attitude was favorable. However, most participants showed poor practices in terms of containing potential virus outbreaks. In our multivariable analyses, people 25 and older (AOR = 1.6, 95%CI; 1.2, 4.6) and those who lived in urban areas (AOR = 4.3, 95%CI; 2.6, 15.8) were significantly associated with being knowledgeable about COVID-19. Moreover, we found that the source of information about COVID-19 (AOR = 2.3, 95%CI; 1.6, 8.7) was significantly associated with the attitude undergraduate students had about COVID-19.Conclusion: The undergraduate students at Debre Berhan University were moderately knowledgeable about COVID-19 and had an optimistic attitude towards its resolution. However, this optimism may be leading to poor public health practices within this community. Therefore, greater efforts need to be made through educational campaigns to inform the public of the necessity for proper practices in containing this disease.