Elevated arterial blood pressure (BP) is associated with autonomic dysfunction and impaired hemodynamic control mechanisms. Isometric exercise (IE) training has been demonstrated effective at reducing BP; however, the continuous cardiovascular responses during IE are underinvestigated. We hypothesized that reflex autonomic cardiovascular control is an important mediator in reducing BP. To test our hypothesis, we investigated continuous cardiac autonomic modulation and baroreceptor reflex sensitivity (BRS) in response to IE. Twenty-five prehypertensive participants performed a single IE wall squat training session. Total power spectral density (PSD) of HR variability (HRV) and associated low-frequency (LF) and high-frequency (HF) power spectral components were recorded in absolute (ms) and normalized units (nu) before, during, and after an IE session. HR was recorded via electrocardiography and BRS via the sequence method. Continuous BP was recorded via the vascular unloading technique and stroke volume via impedance cardiography. Total peripheral resistance was calculated according to Ohm's law. During IE, there were significant reductions in HRV (P < 0.05) and BRS (P < 0.05) and significant increases in HR (P < 0.001), systolic, diastolic, and mean BP (all P < 0.001). In recovery from IE, HRV (P < 0.001), HFnu (P < 0.001), and BRS (P < 0.001) significantly increased with a significant decrease in LFnu (P < 0.001) and LF:HF ratio (P < 0.001), indicative of predominant parasympathetic over sympathetic activity. This autonomic response was associated with a significant reduction in systolic (23.2 ± 18.1 mm Hg, P < 0.001), diastolic (18.7 ± 16.9 mm Hg, P < 0.001), and mean (15.8 ± 15.5 mm Hg, P < 0.001) BP, below baseline and a significant reduction in total peripheral resistance (P < 0.001). A single IE session is associated with improved cardiac autonomic modulation and hemodynamic cardiovascular control in prehypertensive males. These acute responses may be mechanistically linked to the chronic reductions in resting BP reported after IE training interventions.