Air pollution poses a substantial barrier to global environmental sustainability and citizen well-being. However, there is a lack of research that specifically examines the effects of short-term exposure to PM_2.5 and its components on health outcomes in developing nations in Asia. The present study evaluated the associations between PM_2.5 components and hospital admissions (HAs) and emergency room visits (ERVs) for respiratory diseases in a megacity of Karachi, Pakistan. We assessed the lag structure of the excess risk (ER) of the pollutant—outcome association (0-6 single and cumulative lag days) using time-series quasi-Poisson models, after adjusting for temperature, humidity, and day of the week. This first study in Pakistan found that PM_2.5 and its constituents were associated with respiratory HAs and ERVs for the inhabitants of the megacity of Karachi. These associations varied by different PM constituents, disease subtypes, age, and gender. The leading causes for HAs were COPD (21.5%), asthma (17.3%), and TB (12.3%). Asthma (24.4%), TB (18.0%), and COPD (17.3%) were the principal causes of ERVs. Males accounted for 62.0% of the HAs and 58.1% of the ERVs. The prevalence of respiratory diseases increased with age, peaking with the age group 18-64. The highest ERs for all respiratory morbidity were observed for PM_2.5 (10.3, 95% CI: 2.59%-18.59), NH₄⁺ (9.58%, 95% CI: 1.50%-18.30%), air quality index (9.11%, 95%CI: 2.54%-16.09%), and SO₄^2- (7.26%, 95% CI: 1.03%-13.87%) within 0-4 lag days. Additionally, patients with COPD, TB, or other pulmonary diseases, and older or male patients, were more vulnerable to these pollutants. Our results provide important information for policy makers for developing regulations for improving air quality and public health. Further studies are urgently needed in other developing countries to disentangle the effects of air pollution on health.