Background Despite substantial declines in burden over time, stroke remains a public health threat in the Americas. This study aimed to assess the current magnitude, trends, and disparities in the estimates of stroke burden by sex and age in the Americas from 1990 to 2021. Methods Estimates from the Global Burden of Disease, Injuries and Risk Factors Study 2021 were used to analyze incidence, prevalence, mortality, years of life lost due to premature death, years lived with disabilities, and disability- adjusted life years (DALYs) caused by stroke and its major subtypes stratified by age, and sex in the Americas from 1990 to 2021. We used Joinpoint regression analysis to estimate the average annual percent change (AAPC) of stroke mortality and disease burden outcomes and assessed trends. Findings In 2021, there were 1.1 million (95% uncertainty interval: 1.0-1.2) new cases, 12.9 million (12.3-13.7) prevalent cases, 0.5 million (0.5-0.6) deaths, and 11.4 million (10.6-12.1) DALYs due to stroke in the Americas. The absolute number of stroke burden outcomes increased from 1990 to 2021, but their corresponding age-standardized rates significantly declined. A deceleration in reduction rates of burden outcomes for all strokes and most stroke subtypes occurred over the last decade, with pronounced difference between sexes mainly in incidence among younger groups. From 2015 to 2021, trends in incidence rates from all stroke and stroke subtypes reversed to increase in most age groups, and strikingly, trends in mortality and DALY rates from ischemic stroke among younger populations reversed to upward with AAPC over 1.4%. A substantial number of countries contributed to these increasing trends. Interpretation Regionally, the annual number of stroke cases and deaths significantly increased from 1990 to 2021, despite reductions in age-standardized rates. The declining pace in age-standardized stroke rates has decelerated in recent years, while trends in incidence, and ischemic stroke mortality and DALY among middle-aged adults and adults, reversed towards upward in the period 2015-2021. Further studies are needed to understand the determinants of this recent pattern and identify the most cost-effective interventions to stem this alarming trend. Copyright (c) 2025 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND IGO license (http://creativecommons.org/licenses/by-nc-nd/3.0/igo/).