Objective: The interplay of hypertension and obesity is well described. Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). The aim of this review is to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes. Design and method: This systematic review was performed in line with the 2020 PRISMA statement. Relevant studies were identified via a search of MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science. Studies were screened to include randomised controlled trials of semaglutide versus a placebo in adults without diabetes. Continuation of anti-hypertensive treatment was a secondary outcome. Pooled and sensitivity analyses were performed and risk of bias was assessed. Results: 611 potential studies were found by the search and 6 RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in SBP was -4.83 mmHg (95% CI -5.65 to -4.02) while that for DBP was -2.45 mmHg (95% CI -3.65 to -1.24). Only two studies (STEP 1, 4) reported change in anti-hypertensive medications. In STEP 1, 34.3% of those on anti-hypertensive medications, and receiving the intervention, either decreased or stopped these drugs, versus 16% in the placebo group. Equivalent figures were 25.5% and 11.9% for STEP 4. Critical appraisal revealed all included studies to be of a high methodological quality. Conclusions: The magnitude of BP reduction evident following semaglutide treatment in normotensive populations with obesity and without diabetes is clinically significant. The effect of semaglutide in those with obesity and hypertension is yet to be determined. Targeting excess body weight may be a novel therapeutic strategy for patients with difficult to control hypertension.