Prior human and animal research suggests prenatal stress alters developmental systems that support stress and emotion regulation in offspring, which may underlie vulnerability to psychopathology risk. We examined prospective associations between prenatal stress from a natural disaster and infant biobehavioral outcomes across toddlerhood. Women pregnant during Hurricane Harvey in 2017 completed assessments of their objective levels of hardship and their subjective distress from the disaster. Offspring (n = 47) completed follow-up assessments at 24 months to collect autonomic nervous system activity (respiratory sinus arrythmia, RSA; heart rate, HR) during a stressor task. Parents assessed their children’s behavioral problems at 24 and 48 months of age. Increased prenatal subjective distress was associated with a blunted RSA response to stress and less RSA recovery, whereas increased objective hardship was associated with greater HR reactivity and recovery. Prenatal subjective distress was associated with increased child behavior problems at 24 months. Higher behavior problems at 24 months of age were also associated with RSA and HR reactivity and recovery. Findings suggest that prenatal stress is an important predictor of offspring biobehavioral risk. Further research is needed to explore longitudinal pathways.