Mindfulness is known to decrease psychological distress. Possible benefits in pregnancy have rarely been explored. Our aim was to examine the prospective association of mindfulness with autonomic nervous system function during pregnancy and with later infant social-emotional development. Pregnant women (N = 156) completed self-report mindfulness and emotional distress questionnaires, and had their autonomic function assessed in their first and third trimesters, including heart rate (HR), indices of heart rate variability (HRV), preejection period (PEP), and systolic (SBP) and diastolic blood pressure (DBP). The social-emotional development of 109 infants was assessed at 4 months of age. More mindful pregnant women had less prenatal and postnatal emotional distress (p < .001) and higher cardiac parasympathetic activity: root mean square of successive differences (RMSSD: p = .03) and high-frequency (HF) HRV (p = .02). Between the first and third trimesters, women's overall HR increased (p < .001), and HRV (RMSSD, HF HRV, and low-frequency (LF) HRV: p < .001) and PEP decreased (p < .001). In more mindful mothers, parasympathetic activity decreased less (RMSSD: p = .01; HF HRV: p = .03) and sympathetic activity (inversely related to PEP) increased less (PEP: p = .02) between trimesters. Their offspring displayed less negative social-emotional behavior (p = .03) compared to offspring of less mindful mothers. Mindfulness in pregnancy was associated with ANS changes likely to be adaptive and with better social-emotional offspring development. Interventions to increase mindfulness during pregnancy might improve maternal and offspring health, but randomized trials are needed to demonstrate this.