Introduction: The extent to which shifting age distributions, changes in stroke subtypes, and increases in obesity rates have impacted stroke mortality remain uncertain. Hypothesis: We hypothesize strong age and period effects on trends in stroke mortality, with obesity playing an important role in these trends. Methods: We designed a sequential time series analysis of 4,060,259 stroke deaths among women and men aged 18-84 years in the US, 1975-2019. The US annual mortality data, and US mid-year population data were accessed from Our World in Data and the CDC. Mortality rates were examined for overall stroke, and ischemic and hemorrhagic strokes. Trends in stroke mortality based on changes in the distribution of age, period, and birth cohorts (APC) were evaluated from Poisson models. We also aimed to quantify how much of the temporal increase in obesity rates explain the variance in stroke mortality trends. Results: Age-standardized stroke mortality declined for women (87.5 [95% confidence interval , CI, 86.8, 88.1] per 100,000 in 1975 to 30.9 [95% CI, 30.6, 31.2] in 2019) and men (112.1 [95% CI, 111.3, 113.0] per 100,000 in 1975 to 38.7 [95% CI, 38.3, 39.0] in 2019). In an APC analysis, stroke mortality increased sharply with advancing age (Figure). Ischemic and hemorrhagic strokes declined by period. There was a cohort effect for ischemic, but not hemorrhagic stroke. In 2019, the rate ratio (RR) of mortality for men versus women was 1.30 (95% CI, 1.27, 1.33) for ischemic stroke and 1.12 (95% CI, 1.09, 1.15) for hemorrhagic stroke. Increasing rates of obesity accounted for 86% and 80% of the temporal decline in stroke mortality rates among women and men, respectively. Conclusions: In the US, mortality rates from stroke have declined over the last 45 years. While men are more likely to die from stroke, the gender difference has narrowed for ischemic stroke, but widened for hemorrhagic strokes. Obesity appears to have contributed substantially to the decline in stroke mortality.