Adolescent girls in urban areas of Uganda suffer unique challenges that affect their safe transition to adulthood. These challenges include; early school dropout, domestic and sexual violence, child labour and exploitation, limited access to sexual and reproductive health services, among others. These vulnerabilities increase social and economic exclusion and have been exacerbated by the COVID-19 pandemic and the subsequent measures to slow down its spread, for instance, the countrywide lockdown and the school closures. This policy brief provides a snapshot of the unique challenges faced by adolescent girls in urban areas and makes the case for transformative social protection programmes that address structural barriers to the economic and social inclusion of adolescent girls. In light of the findings, the brief recommends the need for community sensitization against sexual and physical abuse, and enforcement of laws to protect adolescent girls in urban settings.