Neighborhood disadvantage has consistently been linked to increased rates of morbidity and mortality, but the mechanisms through which neighborhood environments may get “under the skin” remain largely unknown. Differential exposure to chronic environmental stressors has been identified as a potential pathway linking neighborhood disadvantage and poor health, particularly through the dysregulation of stress-related biological pathways such as cortisol secretion, but the majority of existing observational studies on stress and neuroendocrine functioning have focused exclusively on individual-level stressors and psychosocial characteristics. This paper aims to fill that gap by examining the association between features of the neighborhood environment and the diurnal cortisol patterns of 308 individuals from Chicago, Illinois, USA. We found that respondents in neighborhoods with high levels of perceived and observed stressors or low levels of social support experienced a flatter rate of cortisol decline throughout the day. In addition, overall mean cortisol levels were found to be lower in higher stress, lower support neighborhoods. This study adds to the growing evidence of hypocortisolism among chronically stressed adult populations and suggests hypocortisolism rather than hypercortisolism as a potential mechanism linking social disadvantage to poor health.