Background: Corona Virus Disease-19 is an acute respiratory disease resulted from genetic recombination called severe acute respiratory syndrome corona virus. The disease was declared as global public health emergency. It had global and national consequences like economical crisis, interruptions of schools, psychological distress, stigmatization of infected patients and gender based violence. However, none of previous studies addressed important predictor variables on prevention practices and explored experience of residents. Objective: To assess prevention practices on corona virus disease-19 and associated factors among adult residents in Debre Tabor town, Northwest Ethiopia, 2020. Methods: Community based cross sectional study triangulated with qualitative study was conducted among 778 residents in Debre Tabor town. Study was done from November 30 to December 30/2020 using multistage random sampling techniques. Data were collected using structured interviewer-administered questionnaire and entered in Epi Data (version 4.6) then exported to SPSS (version 23) for analysis. Simple and multiple binary logistic analyses were done using odds ratio with 95% confidence interval. Finally, P-value < 0.05 was considered as significant in multivariate analysis. Six focus group discussions were undertaken based on occupational status, and open code software was used for thematic analysis. Result: The response rate of this study was 762 (97.9%) and the prevalence of good prevention practice was 80 (10.5%) (CI: 8.4-12.9). Educational level, average monthly income, good attitude (AOR=5.669, CI; 2.989-10.753), chronic medical illness (AOR=6.147, CI; 3.190-11.844), source of information and occupational status were significant factors of prevention practices on corona virus disease-19. Lack of preventive materials, low income, lifestyle and working characteristics were factors of prevention. Conclusion: In this study, prevalence of good prevention practices on COVID-19 was lower. Educational level, occupational status, attitude, chronic medical illness, source of information and average monthly incomes were significant factors of prevention practices. Indeed; low income, lack of preventive materials, lifestyle and working characteristics. It is better to develop rules to apply preventive measures in public places and train housewives, merchants and drivers. Keywords: COVID-19, Prevention practices, associated factors, Debre Tabor