This study used a stress biomarker, diurnal cortisol, to identify how elevated stress in mothers of children and adults with autism and other disabilities relates to their health and mental health. Based on semi-parametric, group-based trajectory analysis of 91 mothers, two distinctive cortisol trajectories emerged: blunted (63%) or steep (37%). Mothers in the blunted (vs. steep) trajectory had higher stress levels, lower health ratings, and 89% of mothers of children with autism, and 53% with other disabilities, belonged to this trajectory. Atypical cortisol awakening responses and evening rises were differentially associated with anxiety, depression, health problems and employment status. Stress-reducing interventions are needed for parents of children with autism and other disabilities that include biomarkers as indices of risk or treatment outcome.