This study aimed to investigate national data for a quantitative evaluation of antibiotic usage in Korean children during the pre- and early COVID-19 period. This was a cross-sectional study from 2016 to 2021 of children <18 years, grouped by age (0, 1, 2–4, 5–11, and 12–17 years) and city/province. Systemic antibiotic prescriptions, days of administration, and population by age and region were collected. Days of therapy (DOT)/1000 pediatric inhabitant per day (PID) was used for antibiotic quantitative monitoring. A total of 257,088,265 antibiotic doses were prescribed to 170,309,944 children during the 6-year period. The highest DOT during the entire study period was observed in the 1-year age group, followed by the 2–4- and 0-year age groups. The highest DOT was observed in 2019, with 72.8 DOT/1000 PID in the 1-year age group, which fell to 34.7 DOT/1000 PID in 2020, however, DOT soon increased at similar rates to that in the pre-COVID-19 period. A higher DOT/1000 PID was observed for third-generation cephalosporins in 58.8% of the regions compared to beta-lactam/beta-lactamase inhibitors. To conclude, reductions in antibiotic use during the early COVID-19 pandemic period were not maintained. Further interventions are needed to decrease antibiotic overuse and misuse.