High systolic blood pressure (SBP) is the leading preventable global health risk. As part of the Global Burden of Disease Study 2021, we quantify the SBP-associated burden (relative to a theoretical risk exposure level of 105-115 mmHg) among adults over 25, by age and sex, for 204 countries from 1990 to 2021. Standard GBD Bayesian methods were used to estimate SBP mean, standard deviation and corresponding distribution from 1,116 studies. Meta-analyses of 70 randomized controlled trials and cohorts were used to estimate the relative risks for seven outcomes: ischemic heart disease (IHD), stroke, chronic kidney disease (CKD), atrial fibrillation, aortic aneurysm, peripheral arterial disease (PAD) and hypertensive heart disease. Then, the population attributable fraction and SBP attributable burden were computed with 95% uncertainty intervals (UI). In 2021, 10.9 million deaths (9.2-12.5 million) and 225 million (190 - 259 million) disability-adjusted life years (DALYs) were attributable to elevated SBP worldwide, a decrease, since 1990, of 32% and 30% in age-standardized rates, respectively. In 2021, high SBP accounted for 7.8% of total DALYs; 49.9% (40.6 - 58.2%) of DALYs due to IHD; 57.3% (42.7-68.4%) due to stroke; 24.8% (13.0-36.1%) due to CKD; 30.1% (10.7-47.6%) due to atrial fibrillation; 17.1% (12.9-21.4%) due to aortic aneurysm; 13.0% (2.7-23.8%) due to PAD and 100% of the DALYs due to hypertensive heart disease. Globally, the burden attributable to SBP was higher in men than in women (3,162.9 [2,654.8-3,666.4] vs 2,167.3 [1857.4 -2510.9] age-standardized DALYs per 100,000). Age-standardized DALYs attributable to high SBP were highest in Central Asia and Eastern Europe, rates above six thousand per 100,000. The lowest levels were observed in high-income Asia Pacific, Australasia and Western Europe with less than 1000 DALYs per 100,000. Despite a decrease in age-standardized rates since 1990, high SBP remains a major global health risk with considerable regional variations. Targeted interventions are crucial to address these disparities and reduce SBP-related health impacts.