Background. The purpose of this paper is to investigate the prevalence and context of alcohol use, problem drinking and alcohol-related harm among boys and girls in the slums of Kampala, Uganda. Methods. The Kampala Youth Survey is a cross-sectional study conducted in 2014 among youth (ages 12–18 years) living in the slums of Kampala (n = 1133) who were participating in Uganda Youth Development Link (UYDEL) centers. Chi-square tests were used to determine differences in alcohol use behaviors between 1) gender (boys vs. girls), and 2) alcohol use behaviors between problem drinkers and non-problem drinkers, stratified by gender. Results. Among all participants (n = 1133), the prevalence of any alcohol use in the past 12 months was 31% (n = 346). A higher percentage of girl drinkers reported having sex in the past month, without a condom (57.9%) due to alcohol consumption, compared to boy drinkers (41.9%) ( = 8.09, df = 1, p = 0.005). For girl and boy drinkers, nearly half (49.5% and 44.1%, respectively) met the criteria for problem drinkers, measured using the Cut-Annoyed-Guilty-Eye-Opener (CAGE) questionnaire. Conclusions. The high prevalence of alcohol use and problem drinking among youth, as well as alcohol-related harm, warrant urgent alcohol prevention and intervention strategies, particularly among these underserved girls.