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Background Hypertension has become an important public health concern in the developing world owing to rising prevalence and its adverse impact on ailing health systems. Despite being a modifiable risk factor for cardiovascular disease, hypertension has not received the needed attention in Ghana as a result of various competing interests for scarce health resources. This systematic review and meta-analysis provides a comprehensive and updated summary of the literature on the prevalence of hypertension in Ghana. Methods Major databases such as MEDLINE, EMBASE, and Google Scholar and local thesis repositories were accessed to identify population-based studies on hypertension among Ghanaians. Data extracted from retrieved reports were screened independently by two reviewers. The quality of eligible studies was evaluated and reported. A reliable pooled estimate of hypertension prevalence was calculated utilizing a random-effects model and reported according to the GRADE framework. Additionally, a meta-regression analysis was performed to analyze the contribution of study-level variables to variance in hypertension prevalence. Results In general, a total of 45,470 subjects (n = 22,866 males and 22,604 females) were enrolled from urban (n = 12), rural (n = 8), and mixed populations (n = 7). Blood pressure (BP) was measured across studies according to a validated and clinically approved protocol by trained field workers or healthcare workers including nurses and physicians. A combined total of 30,033 participants across twenty studies reporting on the population prevalence of hypertension were pooled with 10,625 (35.4%) identified to satisfy study criteria for elevated BP. The pooled prevalence across 24 studies was 30.3% (95% CI 26.1–34.8%) after fitting a random effects model. Prevalence of hypertension was 30.1% (95% CI 25.6–36.0%) among females and 34.0% (95% CI 28.5–40.0%) among males. Significant differences in pooled estimates across regions emerged from subgroup comparisons of regional estimates with an increasing trend in the north-to-south direction and with increasing age. Compared to rural settings, the burden of hypertension in urban populations was significantly higher. Age structure and population type accounted for 65.0% of the observed heterogeneity in hypertension estimates. Conclusions The prevalence of hypertension in Ghana is still high. The gap in hypertension prevalence between rural and urban populations is closing especially in elderly populations. These findings must claim the attention of public health authorities in Ghana to explore opportunities to reduce rural hypertension. Systematic review registration The protocol for this review has been published previously with PROSPERO (CRD42020215829).