Background. Self‐medication practice is the use of medicine without consulting health professionals to treat self‐recognized illness by the general population including pregnant women. Inappropriate self‐medication practice during pregnancy may pose harmful consequences for the fetus as well as the mother. There is not given much attention on the practice of self‐medication among pregnant women in our setting. Therefore, this study aimed to assess the prevalence of self‐medication practice and associated factors among pregnant women who attended antenatal care at North Shewa Zone public hospitals. Methods. An institution‐based cross‐sectional study was conducted from June 01, 2022 to July 30, 2022, among 650 pregnant women who attended antenatal care at North Shewa Zone public hospitals. A multistage sampling technique was employed. The questionnaires were pretested. A structured interviewer‐administered questionnaire and reviewed medical records were used for data collection. Epi‐data version 4.6.2 and SPSS version 20 were utilized for data entry and analysis, respectively. Bivariate and multivariable logistic regression was done to identify associated factors, and P values less than 0.05 were considered statistically significant. Results. The prevalence of self‐medication practice among pregnant women was 65.38%. Housewives (AOR = 0.097 95% CI 0.030, 0.310), farmers (AOR = 0.117, 95% CI 0.028, 0.493), people with health insurance (AOR = 0.507, 95% CI 0.300, 0.858), and people in preconception care (AOR = 0.038, 95% CI 0.011–0.135) were less likely to practice self‐medication, while people with primary education (AOR = 3.00, 95% CI 1.217, 7.435), income less than 3,000 birr (AOR = 5.46, 95% CI 1.41, 21.1), participants in the first (AOR = 4.183, 95% CI 2.12, 8.24) and second trimesters (AOR = 2.05, 95% CI 1.18, 3.56), pregnant women who lived in rural areas (AOR = 1.579, 95% CI 1.103–2.260), and people who previously practiced self‐medication (AOR = 8.2, 95% CI 5.04, 13.3) were more likely to practice self‐medication. Conclusion. From the present finding, it can be concluded that self‐medication among pregnant women is high. Previous self‐medication practice, gestation period, educational status, monthly income, no preconception care, no health insurance, being a housewife, farmer, and place of residence were significantly associated with self‐medication practice. Therefore, preventive measures such as proper counseling during dispensing, awareness creation programs on preconception care, and enrolling in health insurance programs to minimize the practice of self‐medication are necessary.