Asthma affects millions of people globally and is especially concerning in populations living with poor air quality. This study examines the association of ambient outdoor air pollutants on asthma-related emergency department (ED) visits in children and adults throughout the Pittsburgh region. A time-stratified case-crossover design is used to analyze the lagged effects of fine particulate matter (PM2.5) and gaseous pollutants, e.g., ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) on asthma-related ED visits (n = 6682). Single-, double-, and multi-pollutant models are adjusted for temperature and analyzed using conditional logistic regression. In children, all models show an association between O3 and increased ED visits at lag day 1 (OR: 1.12, 95% CI, 1.03–1.22, p < 0.05) for the double-pollutant model (OR: 1.10, 95% CI: 1.01-1.20, p < 0.01). In adults, the single-pollutant model shows associations between CO and increased ED visits at lag day 5 (OR: 1.13, 95% CI, 1.00–1.28, p < 0.05) and average lag days 0–5 (OR: 1.22, 95% CI: 1.00–1.49, p < 0.05), and for NO2 at lag day 5 (OR: 1.04, 95% CI: 1.00–1.07, p < 0.05). These results show an association between air pollution and asthma morbidity in the Pittsburgh region and underscore the need for mitigation efforts to improve public health outcomes.