Combustion emissions adversely impact air quality and human health. A multiscale air quality model is applied to assess the health impacts of major emissions sectors in United States. Emissions are classified according to six different sources: electric power generation, industry, commercial and residential sources, road transportation, marine transportation and rail transportation. Epidemiological evidence is used to relate long-term population exposure to sector-induced changes in the concentrations of PM 2.5 and ozone to incidences of premature death. Total combustion emissions in the U.S. account for about 200,000 (90% CI: 90,000–362,000) premature deaths per year in the U.S. due to changes in PM 2.5 concentrations, and about 10,000 (90% CI: −1000 to 21,000) deaths due to changes in ozone concentrations. The largest contributors for both pollutant-related mortalities are road transportation, causing ∼53,000 (90% CI: 24,000–95,000) PM 2.5 -related deaths and ∼5000 (90% CI: −900 to 11,000) ozone-related early deaths per year, and power generation, causing ∼52,000 (90% CI: 23,000–94,000) PM 2.5 -related and ∼2000 (90% CI: −300 to 4000) ozone-related premature mortalities per year. Industrial emissions contribute to ∼41,000 (90% CI: 18,000–74,000) early deaths from PM 2.5 and ∼2000 (90% CI: 0–4000) early deaths from ozone. The results are indicative of the extent to which policy measures could be undertaken in order to mitigate the impact of specific emissions from different sectors — in particular black carbon emissions from road transportation and sulfur dioxide emissions from power generation.