Air pollution’s mortality effects may differ by subpopulation; however, few studies have investigated this issue in Asia. We investigated susceptibility to air pollutants on total, cardiovascular, and respiratory mortality in Seoul, Korea for the period 2000–2007. We applied time-stratified case-crossover analysis, which allows direct modeling of interaction terms, to estimate susceptibility based on sex, age, education, marital status, and occupation. An interquartile range increase in pollution was associated with odds ratios of 0.94 (95% confidence interval, 0.25–1.62), 2.27 (1.03–3.53), 1.94 (0.80–3.09), and 2.21 (1.00–3.43) for total mortality and 1.95 (0.64–3.27), 4.82 (2.18–7.54), 3.64 (1.46–5.87), and 4.32 (1.77–6.92) for cardiovascular mortality for PM10, nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), respectively. Ozone effect estimates were positive, but not statistically significant. Results indicate that some populations are more susceptible than others. For total or cardiovascular mortality, associations were higher for males, those 65–74 years, and those with no education or manual occupation for some pollutants. For example, the odds ratio for SO2 and cardiovascular mortality was 1.19 (1.03–1.37) times higher for those with manual occupations than professional occupations. Our findings provide evidence that some populations are more susceptible to the effects of air pollution than others, which has implications for public policy and risk assessment for susceptible subpopulations.