Associations between urban adolescents’ victimization experiences and biological stress responses were examined, as well as emotion regulation as a moderator of these associations. Data from a 4-wave longitudinal study with a low-income, community-based sample (n = 242; 91 % African American; 57 % female; M = 11.98, SD = 1.56 years at baseline) revealed that victimization, assessed over 3 study waves, was associated with an attenuated cortisol response to a stress interview at the final study wave, indicating that responses of the Hypothalamus–Pituitary–Adrenal (HPA) axis were dysregulated. Cortisol responses were moderated by caregiver-reported adolescent emotion regulation, suggesting that this modifiable protective factor that is taught in many school-based prevention programs could help reduce harm associated with HPA axis dysregulation linked to victimization.