Air pollution is a major environmental health hazard. The WHO estimates that air pollution contributes more than 7 million premature deaths globally on an annual basis. This estimate is not uniformly distributed: more than two third deaths occur in developing countries of South Asia. This study evaluates the health risks of air pollution exposure in a megacity Karachi, Pakistan, using the cigarette-equivalent technique. Sampling of fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and black carbon (BC) was performed at various fixed locations throughout the four seasons of the year. We evaluated the health risks of pollutants exposure using four different health endpoints including low birth weight (<2500 g at term after 37 weeks of gestation), decreased lung function (Forced Expiratory Volume in 1 second), cardiovascular mortality, and lung cancer in residents of Karachi. The average risks of low birth weight from PM_2.5, NO₂, and BC were 37.2, 14.8, and 1.01, respectively, while the average risks of decreased lung function were 93.9, 38.8, and 2.87. Risks of cardiovascular mortality were 51.9, 14.3, and 2.79, and those of lung cancer were 31.3, 6.47, and 1.32, respectively. The remarkably high risks are attributed to high concentrations of air pollutants. These results suggests that residents of Karachi may experience other adverse health effects beyond those typically usually attributed to air pollution.