Background: One of the challenges in medicine has been the exaggerated use of antibiotics. The purpose of this study was to investigate the prevalence of antibiotic usage in children in Arak, Iran (2019-2020) to determine the factors related to antibiotic prescription and consumption in children. Methods: This was a population based, cross-sectional study conducted in Arak, the capital city of Markazi Province, Iran. Stratified random sampling was applied to recruit children who were up to five years old, and registered in the healthcare system between Jan. 2019 and Jan. 2020. A response rate of 85% was obtained from the subjects’ parents. Face-to-face interviews were used to collect the data from the children’s mothers. Univariate and adjusted linear regression analyses were applied to assess the determinants of antibiotic consumption in these children. Results: A total of 1483 children were enrolled in the study; most of them were boys with the mean age of 2.1±1.5 years old. The annual prevalence of antibiotic consumption in Arak was found to be 62.4% for at least one antibiotic. The most consumed antibiotic was azithromycin (24.2%). Among antibiotic groups, the most consumed group was macrolides (26.9%). Upon multiple logistic regression analyses, a lower consumption rate was observed among the younger children with older mothers, and children whose fathers had permanent jobs than other children groups. A higher consumption rate was observed among families with higher parity. Conclusion: The annual prevalence of antibiotic consumption in this study was very high, with the most consumed drug being azithromycin. We recommend that the use of antibiotics be reconsidered by drawing future healthcare policies, aiming at reducing the heavy antibiotics consumption in children.