Understanding patterns of opioid receipt by children and adolescents over time and understanding differences between age groups can help identify opportunities for future opioid stewardship. We conducted a retrospective cohort study, using South Carolina Medicaid data for children and adolescents 0–18 years old between 2000–2020, calculating the annual prevalence of opioid receipt for medical diagnoses in ambulatory settings. We examined differences in prevalence by calendar year, race/ethnicity, and by age group. The annual prevalence of opioid receipt for medical diagnoses changed significantly over the years studied, from 187.5 per 1000 in 2000 to 41.9 per 1000 in 2020 (Cochran–Armitage test for trend,p< 0.0001). In all calendar years, older ages were associated with greater prevalence of opioid receipt. Adjusted analyses (logistic regression) assessed calendar year differences in opioid receipt, controlling for age group, sex, and race/ethnicity. In the adjusted analyses, calendar year was inversely associated with opioid receipt (aOR 0.927, 95% CI 0.926–0.927). Males and older ages were more likely to receive opioids, while persons of Black race and Hispanic ethnicity had lower odds of receiving opioids. While opioid receipt declined among all age groups during 2000–2020, adolescents 12–18 had persistently higher annual prevalence of opioid receipt when compared to younger age groups.