Anemia during pregnancy is a public health problem and is related to negative birth outcomes, especially in developing countries. The main aim of this study was to assess predictors of anemia among pregnant women attending antenatal clinics at Hiwot Fana Comprehensive Specialized University Hospital, Eastern Ethiopia. Unmatched case-control study design was employed among 352 individuals. A face-to-face interview was used to gather data, and each pregnant woman's antenatal care follow-up record cards were reviewed in addition to the interview. EpiData version 3.1 and IBM SPSS version 26 was used for data entry and analysis, respectively. Bivariable and multivariable analyses were conducted to identify predictors of anemia, a p-value of <0.05 was considered a statistically significant association. The common determinants for anemia in pregnant mothers were: rural residency (AOR=2.25, 95% CI: 1.14-4.8), no formal education (AOR=4.4, 95% CI: 1.94-9.9), inter-pregnancy interval (AOR=2.7, 95% CI: 1.24-5.8), and mid-upper arm circumference (AOR=5.0, 95% CI: 2.0-12.7). In this study, the identified determinant factors for anemia were: rural residency, maternal educational status, inter-pregnancy-interval, and mid-upper arm circumference. Therefore, providing health education and promotion for pregnant women regarding anemia by focusing on rural residents and counseling to lengthen their birth spacing is an important task. Moreover, counseling on taking iron supplementation as suggested and consuming a diet rich in iron during antenatal care will be recommended.