Background: Air quality is an important determinant of cardiovascular health such as ischemic heart disease and acute ischemic stroke (AIS) with substantial mortality and morbidity reported across the globe. However, associations between air quality and AIS in the current literature remain inconsistent, with few studies undertaken in cosmopolitan cities located in the tropics. Objectives: We evaluated the associations between individual ambient air pollutants and AIS. Methods: We performed a nationwide, population-based, time-stratified case-crossover analysis on all AIS cases reported to the Singapore Stroke Registry from 2009 to 2018. We estimated the incidence rate ratio (IRR) of AIS across different concentrations of each pollutant by quartiles (referencing the 25th percentile), in single-pollutant conditional Poisson models adjusted for time-varying meteorological effects. We stratified our analysis by predetermined subgroups deemed at higher risk. Results: A total of 51,675 episodes of AIS were included. Ozone (O₃) (IRR_{4th quartile}: 1.05, 95% confidence interval (CI): 1.01–1.08) and carbon monoxide (CO) (IRR_{2nd quartile}: 1.05, 95% CI: 1.02–1.08, IRR_{3rd quartile}: 1.07, 95% CI: 1.04–1.10, IRR_{4th quartile}: 1.07, 95% CI: 1.04–1.11) were positively associated with AIS incidence. The increased incidence of AIS due to O₃ and CO persisted for 5 days after exposure. Those under 65 years of age were more likely to experience AIS when exposed to CO. Individuals with atrial fibrillation (AF) were more susceptible to exposure from O₃, CO, and PM₁₀. Current/ex-smokers were more vulnerable to the effect of O₃. Conclusion: Air pollution increases the incidence of AIS, especially in those with AF and in those who are current or ex-smokers.