This study compared the effects of lower- versus higher-intensity isometric handgrip exercise on resting blood pressure (BP) and associated clinical markers in adults with hypertension. Thirty-nine males were randomly assigned to one of three groups, including isometric handgrip at 60% maximal voluntary contraction (IHG-60), isometric handgrip at 30% IHG-30, or a control group (CON) that had been instructed to continue with their current activities of daily living. The volume was equated between the exercise groups, with IHG-60 performing 8 × 30-s contractions and IHG-30 performing 4 × 2-min contractions. Training was performed three times per week for 8 weeks. Resting BP (median [IQR]), flow-mediated dilation, heart rate variability, and serum markers of inflammation and oxidative stress were measured pre- and post-intervention. Systolic BP was significantly reduced for IHG-60 (−15.5 mmHg [−18.75, −7.25]) and IHG-30 (−5.0 mmHg [−7.5, −3.5]) compared to CON (p < 0.01), but no differences were observed between both the exercise groups. A greater reduction in diastolic BP was observed for IHG-60 (−5.0 mmHg [−6.0, −4.25] compared to IHG-30 (−2.0 mmHg [−2.5, −2.0], p = 0.042), and for both exercise groups compared to CON (p < 0.05). Flow-mediated dilation increased for both exercise groups versus CON (p < 0.001). IHG-30 had greater reductions in interleukin-6 and tumor necrosis factor-α compared to the other groups (p < 0.05) and CON (p = 0.018), respectively. There was a reduction in Endothelin-1 for IHG-60 compared to CON (p = 0.018). Both the lower- and higher-intensity IHG training appear to be associated with reductions in resting BP and improvements in clinical markers of inflammation and oxidative stress.