This study investigated cardiovascular variability and stress reactivity in major depressive disorder (MDD). While previous research has documented reduced heart rate variability, knowledge about blood pressure variability in MDD remains scarce. Regarding reactivity, a particular focus was placed on the time courses of the cardiovascular responses, which may provide insight into the autonomic mechanisms underlying the hypo-reactivity expected in MDD. In 76 MDD patients and 71 healthy controls, blood pressure was continuously recorded at rest and during mental stress induced by a 3-min serial subtraction task. Compared to controls, patients exhibited lower systolic and diastolic blood pressure, heart rate variability, and systolic and diastolic blood pressure variability. Moreover, smaller stress-related changes in heart rate, systolic and diastolic blood pressure, and sensitivity of the cardiac baroreflex arose in patients. Cardiovascular parameters did not differ between patients using antidepressants and unmedicated patients. According to time-course analysis, reduced hemodynamic modulations in MDD mainly occurred after 50 s of the stress period. Low heart rate variability in MDD reflects deficient top-down integration of the brain mechanisms allowing flexible autonomic and behavioral control; diminished blood pressure variability is indicative of poor homeostatic capacity with respect to the regulation of blood pressure and organ perfusion. Moreover, blunted cardiovascular reactivity implies poor adjustment of energetic resources to internal and environmental demands and may be a correlate of deficient motivational dynamics characterizing MDD. While cardiovascular hypo-reactivity in MDD may be mediated by baroreflex and adrenergic mechanisms, the fast-acting parasympathetic system may play a subordinate role.