Isometric exercise training (IET) effectively reduces resting blood pressure (BP). Traditionally, IET protocols use hand grip or leg extension exercise. IET using larger muscle mass may influence the rate and magnitude of BP reductions. This study aimed to examine the efficacy of a novel isometric wall squat protocol. Twenty participants completed four laboratory visits over 2 wk. Two incremental isometric wall squat exercise (IWSE) tests were completed to determine the relationship of knee joint angle to heart rate (HR) and BP. The incremental IWSE test started at 135° of knee flexion decreasing by 10° every 2 min until 95° (final stage). Exercise was terminated upon completion of the 10-min test or at volitional fatigue. To ascertain the efficacy of prescribing IWSE training, the relationship between knee joint angle and mean HR was used to calculate the participant-specific knee joint angle required to elicit a target HR of 95% HRpeak for 2× IWSE training sessions. There were inverse relationships (P < 0.05) between knee joint angle and mean HR/BP parameters (r ≥ −0.99), with no difference in the peak HR during the last 30 s of the two incremental tests (P > 0.05). Although there were no differences (P > 0.05) in mean HR and BP values between repeated training sessions, there were differences (P < 0.05) within and between the four bouts during a session. In conclusion, data indicate that the IWSE test provides a reliable means of prescribing and monitoring isometric exercise intensity. The ability of IWSE to reduce resting BP when used for isometric exercise training prescription has been demonstrated in healthy participants. This finding could be significant in the nonpharmacological prevention, treatment, and management of hypertension.