© 2020 The Author(s). Background: The highest burden of hypertension is found in Sub-Saharan Africa (SSA) with a threefold greater mortality from stroke and other associated diseases. Ethnicity is known to influence the response to antihypertensives, especially in black populations living in North America and Europe. We sought to outline the impact of all commonly used pharmacological agents on both blood pressure reduction and cardiovascular morbidity and mortality in SSA. Methods: We used similar criteria to previous large meta-analyses of blood pressure agents but restricted results to populations in SSA. Quality of evidence was assessed using a risk of bias tool. Network meta-analysis with random effects was used to compare the effects across interventions and meta-regression to explore participant heterogeneity. Results: Thirty-two studies of 2860 participants were identified. Most were small studies from single, urban centres. Compared with placebo, any pharmacotherapy lowered SBP/DBP by 8.51/8.04 mmHg, and calcium channel blockers (CCBs) were the most efficacious first-line agent with 18.46/11.6 mmHg reduction. Fewer studies assessing combination therapy were available, but there was a trend towards superiority for CCBs plus ACE inhibitors or diuretics compared to other combinations. No studies examined the effect of antihypertensive therapy on morbidity or mortality outcomes. Conclusion: Evidence broadly supports current guidelines and provides a clear rationale for promoting CCBs as first-line agents and early initiation of combination therapy. However, there is a clear requirement for more evidence to provide a nuanced understanding of stroke and other cardiovascular disease prevention amongst diverse populations on the continent. Trial registration: PROSPERO, CRD42019122490. This review was registered in January 2019.