BACKGROUND: After the US coronavirus disease 2019 outbreak, overall prescription dispensing declined but then rebounded. Whether these same trends occurred for children is unknown. METHODS: Using the IQVIA National Prescription Audit, which contains monthly dispensing counts from 92% of US retail pharmacies, we assessed changes in the monthly number of prescriptions dispensed to US children aged 0 to 19 years during 2018-2020. We compared dispensing totals in April to December 2020 and April to December 2019 overall, by drug class, and among drug classes that typically treat acute infections (eg, antibiotics) or chronic diseases (eg, antidepressants). RESULTS: Between January 2018 and February 2020, the median monthly number of prescriptions dispensed to children was 25 744 758. Dispensing totals declined from 25 684 219 to 16 742 568 between March and April 2020, increased to 19 657 289 during October 2020, and decreased to 15 821 914 during December 2020. Dispensing totals during April to December 2020 (160 630 406) were 27.1% lower compared with April to December 2019 (220 284 613). Among the 3 drug classes accounting for the most prescriptions in 2019, the corresponding percentage changes were -55.6% for antibiotics, -11.8% for attention-deficit/hyperactivity disorder medications, and 0.1% for antidepressants. Among drug classes that typically treat acute infections and chronic diseases, percentage changes were -51.3% and -17.4%, respectively. CONCLUSIONS: Prescription dispensing to children declined by one-quarter in April to December 2020 compared with April to December 2019. Declines were greater for infection-related drugs than for chronic disease drugs. Decreased dispensing of the latter is potentially concerning and warrants further investigation. Whether reductions in dispensing of infection-related drugs are temporary or sustained will be important to monitor going forward.