Background. Anemia defined as a low blood hemoglobin concentration is public health importance. The adolescence age group is the most neglected in public health and nutrition research as priorities are usually given to pregnant women, lactating mothers, and their children less than 2 years. Current Ethiopian Food and Nutrition policy included adolescent girls in the most at-risk group for nutritional demands; however, only a few published studies have assessed a deficiency of anemia and associated factors to tackle the intergenerational cycle of malnutrition. Objective. To assess the prevalence of anemia and associated factors among high school adolescent girls in Jimma town. Methods. Data were collected from 528 secondary school adolescent girls by a school-based cross-sectional study design in Jimma town from 1/1/2019 to 1/2/2019, southwest Ethiopia. A multistage sampling technique was used to select the study participants. A portable battery-operated HemoCue Hb 301+ analyzer was used to measure the hemoglobin level, and then reading was classified as normal Hb ≥ 12 g\dl and anemic if the hemoglobin value <12 g/dl based on the WHO 2011 recommended cutoff points after adjustments to altitude was made. Bivariate analysis at p value ≤0.25 was considered as a candidate for multivariable logistic regression. Multivariable logistic regression was done to control for confounders and to identify factors independently associated with anemia. Level of statistical significance was declared at p<0.05. Results. A total of 528 adolescent girls were included in the study yielding a response rate of 95.8%. The prevalence of anemia was found to be 26.7%, 95% CI (22.7, 30.50). In multivariate logistic regression analysis, those living separately from their family (AOR = 4.430, 95% CI (2.20, 8.90)), low dietary diversity score (AOR = 3.57, 95% CI (1.88, 6.75)), menstrual bleeding more than 5 days (AOR = 2.25, 95% CI (1.17, 4.33)), and low economic status (AOR = 2.16, 95% CI (1.17, 4.33)) were positively associated factors with anemia and only having at least a secondary school in mother’s educational status AOR = 0.43, 95% CI (0.18, 0.97) was negatively associated with anemia in the study area. Conclusion. Prevalence of anemia among school adolescent girls was moderate public health importance according to the World Health Organization prevalence estimation of anemia. The living condition of the adolescent girls, dietary diversity score, duration of menses, and low economic status were positive predictor variables, whereas mothers who are being secondary school and above was a protective factor for anemia. Therefore, iron-rich and diversified food consumption should be given attention.