Air pollution is a major environmental health concern in France and around the world. Numerous toxicological and epidemiological studies highlight the many harmful effects of outdoor air pollution on health. A quantitative assessment of the health impacts of ambient air pollution was conducted in the Auvergne-Rhône-Alpes region to enable local stakeholders, by providing results at various geographic scales, to measure the potential benefits of improved air quality on mortality and various health indicators within their territory. This is the first study of its kind conducted at the regional level in France. To estimate the average population exposure to air pollution across all municipalities in the region, concentrations of PM2.5, NO2, and ozone derived from fine-scale modeling (2016–2018) were linked to population data. The study shows that 7% of mortality in the region is attributable to long-term exposure to fine particulate matter, a tracer pollutant from multiple sources, representing approximately 4,300 deaths per year. The results regarding morbidity show that more than 4% of lung cancers, 6% of strokes, and 5% of emergency room visits for asthma in children are attributable to chronic exposure to fine particulate matter. The share attributable to NO2, a tracer pollutant from road traffic, amounts to just under 2,000 deaths, or 3% of annual mortality, and ozone is estimated to be responsible each year, among people aged 65 and older, for 0.6% of hospitalizations due to respiratory causes and approximately 1% of hospitalizations due to cardiovascular causes. These results confirm the significant impact of ambient air pollution on the health of the region’s population and underscore the importance of strengthening efforts to improve air quality, particularly at the local level.