Abstract Background The Coronavirus disease 2019 outbreak is the first reported case in Wuhan, China in December 2019 and suddenly became a major global health concern. Currently, there is no vaccine and treatment have been reported. The aim of this study was to assess the knowledge, attitude, and practice of COVID-19 among chronic disease patients. Methods A hospital-based cross-sectional study was conducted among 422 chronic disease patients from July 01 to August 30, 2020 at Aksum Hospital, Northern Ethiopia. Both bivariable and multivariable logistic regression analyses with 95% confidence intervals were fitted to identify factors associated with poor knowledge and practice towards COVID-19. The adjusted odds ratio (AOR) was used to determine the prevalence of the association between the dependent and independent variables. A P-value