Animal models have shown that chronic stress increases cortisol, which contributes to overeating of highly palatable food, increased abdominal fat and lower cortisol reactivity. Few studies in humans have simultaneously examined these trajectories. We examined premenopausal women, either mothers of children with a diagnosis of an autism spectrum disorder (n = 92) or mothers of neurotypical children (n = 91). At baseline and 2-years, we assessed hair cortisol, metabolic health, and reward-based eating. We compared groups cross-sectionally and prospectively, accounting for BMI change. Caregivers, relative to controls, had lower cumulative hair cortisol at each time point, with no decreases over time. Caregivers also had stable levels of poor metabolic functioning and greater reward-based eating across both time points, and evidenced increased abdominal fat prospectively (all ps ≤.05), independent of change in BMI. This pattern of findings suggest that individuals under chronic stress, such as caregivers, would benefit from tailored interventions focusing on better regulation of stress and eating in tandem to prevent early onset of metabolic disease, regardless of weight status.