Particulate air pollution is becoming a serious public health concern in urban cities in India due to air pollution-related health effects associated with disability-adjusted life years (DALYs) and economic loss. To obtain the quantitative result of health impact of particulate matter (PM) in most populated Mumbai City and most polluted Delhi City in India, an epidemiology-based exposure–response function has been used to calculate the attributable number of mortality and morbidity cases from 1991 to 2015 in a 5-year interval and the subsequent DALYs, and economic cost is estimated of the health damage based on unit values of the health outcomes. Here, we report the attributable number of mortality due to PM10 in Mumbai and Delhi increased to 32,014 and 48,651 in 2015 compared with 19,291 and 19,716 in year 1995. And annual average mortality due to PM2.5 in Mumbai and Delhi was 10,880 and 10,900. Premature cerebrovascular disease (CEV), ischemic heart disease (IHD), and chronic obstructive pulmonary disease (COPD) causes are about 35.3, 33.3, and 22.9% of PM2.5-attributable mortalities. Total DALYs due to PM10 increased from 0.34 million to 0.51 million in Mumbai and 0.34 million to 0.75 million in Delhi from average year 1995 to 2015. Among all health outcomes, mortality and chronic bronchitis shared about 95% of the total DALYs. Due to PM10, the estimated total economic cost at constant price year 2005 US$ increased from 2680.87 million to 4269.60 million for Mumbai City and 2714.10 million to 6394.74 million for Delhi City, from 1995 to 2015, and the total amount accounting about 1.01% of India’s gross domestic product (GDP). A crucial presumption is that in 2030, PM10 levels would have to decline by 44% (Mumbai) and 67% (Delhi) absolutely to maintain the same health outcomes in year 2015 levels. The results will help policy makers from pollution control board for further cost–benefit analyses of air pollution management programs in Mumbai and Delhi.