A mathematical modeling study evaluated the biomedical and behavioral drivers of HIV incidence decline among adolescent girls and young women (AGYW) aged 15–24 years in Uganda based on data from the Rakai Community Cohort Study. The incidence of HIV fell from 1.57 to 0.45 per 100 person-years, the largest decline of any age group for women. An increase in age at first sex (by about 3 years for women and 2 years for men) was a major factor for girls 15–19 years, averting 17% of cumulative infections in 2000–2020 and 37% by 2050. Among women 20–24 years, ART averted 24% of infections by 2020 and 43% by 2050. Voluntary Medical male circumcision (VMMC) has contributed slightly to the historical decline, but has a larger impact in the longer term. ART, VMMC and delay of first sex act additively to reduce incidence. Limitations include self-reported sexual behavior and a model that does not capture the full dynamics of sexual networks. Sustaining the decline requires maintaining behavioral changes and biomedical interventions.