Background: Improving hypertension control is an important global health priority yet, to our knowledge, there is no direct evidence on the blood pressure (BP)-mortality relationship in sub-Saharan Africa. We investigate the BP-mortality relationship in South Africa and assess the comparative effectiveness of different care targets for clinical care and population-wide hypertension management efforts. Methods: We use country-wide population-based longitudinal data from five waves (2008 - 2017) of the South African National Income Dynamics Study (N = 4,993). We estimate the relationship between systolic BP (SBP) and six-year all-cause mortality and compare the mortality reductions associated with lowering SBP to different targets. We then estimate the number needed to treat to avert one death (NNT) under different hypothetical population-wide scale up scenarios. Findings: We found a weak, nonlinear, SBP-mortality relationship with larger incremental mortality benefits at higher SBP values: reducing SBP from 160 to 150 mmHg was associated with a mortality risk ratio of 0.95 (95% CI: 0.90, 0.99, p = 0.033), incrementally reducing SBP from 150 to 140 mmHg a risk ratio of 0.96 (95% CI: 0.91, 1.01, p = 0.12), with no evidence of incremental benefits of reducing BP below 140 mmHg. At the population level, reducing SBP to 150 mmHg among all those with an SBP > 150 mmHg had the lowest NNT (50) at 3.3 deaths averted (95% CI: -0.6, 0.3) per 1,000 population while requiring BP management for 16% (95% CI: 15.2, 17.3) of individuals. Interpretation: The SBP-mortality association is weaker in South Africa than in high-income and many low- and middle-income countries. As such, we do not find compelling evidence in support of targets below 140 mmHg and find that scaling up management based on a 150 mmHg target is more efficient in terms of the NNT compared to strategies to reduce SBP to lower values.