Alcohol-related harms may be increased among adolescent girls and young women (AGYW) involved in sex work, yet data on alcohol misuse among AGYW in sub-Saharan Africa are still scarce. We conducted a cross-sectional study among 15–24-year-old AGYW from January 2013 to December 2018 in Kampala, Uganda and used the Alcohol Use Disorder Identification Test (AUDIT) to study alcohol use patterns and dependence symptoms (dependence score ≥4). Of 1440 participants (median age 21 years), 83.1% had less than secondary education, 79.8% reported ≥10 paying sexual partners in the past month, 46.0% had ever experienced intimate partner violence (IPV), and 20.6% were living with HIV. Overall, 59.9% scored ≥8 and 29.4% scored ≥16 on the AUDIT. Of 277 (15.8%) with dependence symptoms, 69.1% were screened alcohol dependent. An AUDIT score ≥8 was associated with older age, illicit drug use, experiencing IPV, inconsistent condom use with paying partners, and HIV sero-negativity. All factors remained associated with a higher score ≥16 except HIV status. Similarly, illicit drug use, experiencing IPV and inconsistent condom use were associated with dependence symptoms and, in addition, a higher number of paying sexual partners. Alcohol misuse is high in this population, they urgently need harmful substance use reduction interventions.