BACKGROUND: We determined the prevalence of and risk factors for alcohol misuse and illicit drug use among young Ugandans in fishing communities, a recognised "key population" for human immunodeficiency virus (HIV) infection. METHODS: We conducted a cross-sectional survey among young people (15-24 years) in fishing communities in Koome, Uganda, in December 2017-July 2018. Using Audio-Assisted Self-Interviewing, we collected data on socio-demographic characteristics and alcohol use, including the Alcohol Use Disorders Identification Test (AUDIT) and timeline follow-back calendar (TLFB). Blood samples were analysed for HIV, herpes simplex virus 2 (HSV2), and Phosphatidyl ethanol (PEth 16:0/18:1). Urine samples were analysed for illicit drugs. RESULTS: Among 1281 participants (52.7% male, mean age 20 years), 659 (51.4%) reported ever drinking alcohol, 248 (19.4%) had 12-month-AUDIT ≥ 8, and 261 (20.5%) had whole-blood PEth 16:0/18:1 concentration ≥ 20 ng/mL, indicating significant consumption. In multivariable analyses, PEth 16:0/18:1 ≥ 20ng/mL, AUDIT ≥ 8 and binge drinking (≥6 standard drinks per drinking occasion in the previous month from TLFB) were all strongly associated with older age, low education, smoking, and HSV2. Illicit drug use prevalence was 5.2% and was associated with older age, low education, being single, and smoking. CONCLUSION: Levels of alcohol misuse were high among young people in fishing communities and associated with HSV2, a proxy for risky sexual behaviour. Alcohol and illicit drug harm reduction services and HIV prevention programs in Uganda should prioritise young fisherfolk.