High systolic blood pressure (HSBP) is associated with several metabolic and non-metabolic disorders. This research aimed to document the deaths and disability-adjusted life-years (DALYs) attributable to HSBP in the Middle East and North Africa (MENA) region between 1990 and 2019, by age, sex, underlying cause and socio-demographic index (SDI). We used the methodological framework and data drawn from the Global Burden of Disease study 2019 to identify the burden of diseases attributable to HSBP, from 1990 to 2019, in the MENA region. The estimates reported were presented as counts, population-attributable fractions, and age-standardised rates (per 100,000), along with 95% uncertainty intervals. In 2019, 803.6 thousand (687.1 to 923.8) deaths were attributed to HSBP in MENA, which accounted for 25.9% (22.9–28.6%) of all deaths. The number of regional DALYs caused by HSBP in 2019 was 19.0 million (16.3–21.9 million), which accounted for 11.6% (10.1–13.3%) of all DALYs, and was 23.4% (15.9–31.5%) lower than in 1990. The highest age-standardised DALY rate for 2019 was observed in Afghanistan, with the lowest in Kuwait. Additionally, the DALY rate in MENA rose with age for both sexs. Furthermore, a negative linear relationship was found between SDI and the age-standardised DALY rates. The region has a substantial HSBP-related burden. Policymakers and healthcare professionals should prioritize interventions that effectively promote the early detection of HSBP, access to quality healthcare, and lifestyle modifications to mitigate the HSBP burden in the MENA countries.