Introduction: Anemia affects around 38.2% and 22% of pregnant women at a global and national level respectively. In developing countries, women start pregnancy with already depleted body stores of iron and other vitamins with significant variation of anemia within and between regions. Objective: To identify the determinants of anemia among pregnant mothers attending antenatal care in Dessie town health facilities, northern central Ethiopia. Methods: A health facility based unmatched case control study was conducted among 112 cases and 336 controls from January to March 2016 G.C. The sample size was determined by using Epi Info version 126.96.36.199. Study subjects were selected using consecutive sampling technique. Data were collected using a structured questionnaire, entered using Epi Data version 3.1 and analyzed using SPSS version 20. Bivariable and multivariable logistic regression model was used to see the determinants of anemia. Adjusted odds ratio (AOR) with 95% confidence interval (CI) and p-value<0.05 were used to see the significant association. Results: Failure to take dark green leafy vegetables per two weeks (AOR = 5.02, 95% CI: 2.16, 11.71), didn't take chicken per two weeks (AOR = 2.68, 95% CI: 1.22, 5.86), 1st trimester (AOR = 2.07, 95% CI: 1.12, 3.84), 3rd trimester (AOR = 2.96, 95% CI: 1.53, 5.72), HIV infection (AOR = 6.78, 95% CI: 2.28, 20.18) and medication (AOR = 3.57 95% CI: 1.60, 7.98) were positively associated with anemia. Conclusions: Inadequate intake of dark green leafy vegetables, inadequate consumption of chicken, trimester of the current pregnancy, HIV infection and medication were the determinants of anemia among pregnant women. Therefore, anemia prevention strategy should include promotion of adequate intake of dark green leafy vegetables and chicken, increase meal pattern during the entire pregnancy and strengthen the prevention of mother to child HIV transmission/antenatal care programs.