Emissions of fine particulate matter (PM _2.5 ) from human activities have been linked to substantial disease burdens, but evidence regarding how reducing PM _2.5 at its sources would improve public health is sparse. We followed a population-based cohort of 2.7 million adults across Canada from 2007 through 2016. For each participant, we estimated annual mean concentrations of PM _2.5 and the fractional contributions to PM _2.5 from the five leading anthropogenic sources at their residential address using satellite observations in combination with a global atmospheric chemistry transport model. For each source, we estimated the causal effects of six hypothetical interventions on 10-y nonaccidental mortality risk using the parametric g-formula, a structural causal model. We conducted stratified analyses by age, sex, and income. This cohort would have experienced tangible health gains had contributions to PM _2.5 from any of the five sources been reduced. Compared with no intervention, a 10% annual reduction in PM _2.5 contributions from transportation and power generation, Canada’s largest and fifth-largest anthropogenic sources, would have prevented approximately 175 (95%CI: 123–226) and 90 (95%CI: 63–117) deaths per million by 2016, respectively. A more intensive 50% reduction per year in PM _2.5 contributions from the two sources would have averted 360 and 185 deaths per million, respectively, by 2016. The potential health benefits were greater among men, older adults, and low-income earners. In Canada, where PM _2.5 levels are among the lowest worldwide, reducing PM _2.5 contributions from anthropogenic sources by as little as 10% annually would yield meaningful health gains.