The toxic stress model posits that extended activation of stress response systems in the absence of a supportive relationship with an adult may over time lead to physiological alterations to these same systems, and ultimately to poorer physical and mental health outcomes. However, empirical tests of model hypotheses in adolescence, a critical period of development, are lacking. This study expands the toxic stress model to include more developmentally-appropriate risk and protective factors for adolescents experiencing overwhelming and uncontrollable stressors. Data were collected for a study of early adolescents from urban low-income households (N = 101; 10-12 years old; 59% female). Participants and a caregiver completed questionnaires; youths completed the modified Trier Social Stress Task alone and provided six saliva samples. Using latent profile analysis, three profiles of cortisol reactivity were identified in early adolescents exposed to chronic environmental stress: Elevated and Reactive (11%), Moderate and Non-Reactive (26%), and Blunted and Non-Reactive (63%). In accordance with the toxic stress model, exposure to more community violence and less family support were associated with blunted cortisol reactivity, and Reactive profile membership was associated with fewer trauma symptoms. Overall, the findings provide empirical support for the extension of the toxic stress model in early adolescence through the application of developmentally-sensitive measures and provide implications for future interventions.