Background:The novel coronavirus disease 2019 (COVID-19) pandemic has infected over one million individuals with almost 50,000 deaths worldwide. COVID-19 is currently a global health threat and a public health emergency. Therefore, accurate and up-to-date information regarding prevention and control methods is essential. Objective: The aim of the study was to assess the effects of fear and knowledge of COVID-19 on preventive practices among pregnant women who attend antenatal care in northwest Ethiopia, 2020. Methods: An institution-based cross-sectional study was conducted between July and August 2020. The systematic random sampling technique was used to select 422 participants. Data collected by a face to face interview on pretested and structured questions were entered using Epi-Info version 7 and it was analyzed using SPSS version 22 software. The bivariate and multivariable logistic regression model was used to assess factors associated with COVID-19 preventive practices. Adjusted odds ratio (OR) with a 95% confidence interval (CI) was used to determine the association between covariates and the outcome variable. The p-value less than 0.05 was considered statically significant. Results: According to this study, good preventive practice of COVID-19 among pregnant women was found to be (47.4%). Fear of COVID-19 was (50.9%). The majority (55.0%) of the respondents had good knowledge. Fear [AOR: 2.485, 95% CI: (1.664-3.711)] and having good knowledge [AOR: 2.308, 95% CI: (1.541-3.457)] were significantly associated with good prevention practices among the women. Conclusion and Recommendation:Only half of the pregnant women had good preventive practice. The findings suggest that healthcare bodies should consider these findings to develop strategies for preventive practice against COVID-19.