Background <p>Stroke is a leading cause of premature death worldwide. Spatial-temporal characteristics are important for evidence-based stroke care planning and resource allocation. However, long-term global variations of stroke are still lacking.</p> Objective <p>To identify the characteristics of the global spatial distribution of age-standardized mortality rate (ASMR) due to stroke during 2000–2021, thereby informing the efficient allocation of global health care resources.</p> Methods <p>Based on age-standardized mortality rate (ASMR) due to stroke from the Global Health Estimates database, we analyzed stroke variation from 2000 to 2021 in 183 countries worldwide using Moran’s I, Getis-Ord Gi*, and Standard Deviation Ellipse. We stratified the 183 countries into different income groups according to World Bank classification to identify the socioeconomic influence on stroke mortality.</p> Results <p>The result showed that ① From 2000 to 2021, the number of stroke deaths increased worldwide, but the AMSR due to stroke showed a downward trend; ② The spatial distribution of the global AMSR due to stroke varies across geographic regions. with the highest in Asia and southern Africa, and the lowest in Europe and North America; ③ The spatial pattern of hot and cold spots of AMSR due to stroke remained relatively stable from 2000 to 2021, with the greatest changes in Africa and Asia; ④ Generally, countries belong to higher economic groups have lower stroke mortality rate, and this pattern persisted throughout the study period.</p> Conclusions <p>Our findings provide evidence on spatial variations of stroke mortality worldwide over 20 years, and are informative on evidence-based allocation of medical resources globally.</p> Clinical trial number <p>Not applicable.</p>