Mounting epidemiological evidence has documented the associations between long-term exposure to multiple air pollutants and increased mortality. There is a pressing need to determine whether risks persist at low concentrations including below current national standards. Air pollution levels have decreased in the United States, and better understanding of the health effects of low-level air pollution is essential for the amendment of National Ambient Air Quality Standards (NAAQS). A nationwide, population-based, open cohort study was conducted to estimate the association between long-term exposure to low-level PM, NO, O, and all-cause mortality. The study population included all Medicare enrollees (ages 65 years or older) in the contiguous U.S. from 2001 to 2017. We further defined three low-exposure subcohorts comprised of Medicare enrollees who were always exposed to low-level PM (annual mean ≤12-μg/m), NO (annual mean ≤53-ppb), and O (warm-season mean ≤50-ppb), respectively, over the study period. Of the 68.7-million Medicare enrollees, 33.1% (22.8-million, mean age 75.9 years), 93.8% (64.5-million, mean age 76.2 years), and 65.0% (44.7-million, mean age 75.6 years) were always exposed to low-level annual PM, annual NO, and warm-season O over the study period, respectively. Among the low-exposure cohorts, a 10-μg/m increase in PM, 10-ppb increase in NO, and 10-ppb increase in warm-season O, were, respectively, associated with an increase in mortality rate ranging between 10 and 13%, 2 and 4%, and 12 and 14% in single-pollutant models, and between 6 and 8%, 1 and 3%, and 9 and 11% in tripollutant models, using three statistical approaches. There was strong evidence of linearity in concentration-response relationships for PM and NO at levels below the current NAAQS, suggesting that no safe threshold exists for health-harmful pollution levels. For O, the concentration-response relationship shows an increasingly positive association at levels above 40-ppb. In conclusion, exposure to low levels of PM, NO, and warm-season O was associated with an increased risk of all-cause mortality.