Polycyclic aromatic hydrocarbons (PAHs) are of high concern to public health due to their carcinogenic and mutagenic properties. Here, we present the first comprehensive and quantitative analysis of sources, potential source regions according to source sectors and source-related human health risks of multi-year atmospheric measurements of PAHs in the Canadian Great Lakes Basin (GLB). The highest PAH concentrations were observed at a rural residential site (Egbert), followed by two regionally representative remote sites [Point Petre (PPT) and Burnt Island]. The levels of most PAHs in the GLB atmosphere significantly decreased between 1997 and 2017, broadly consistent with the decreasing trends of anthropogenic emissions. Coal, liquid fossil fuel, and biomass burning were the most common potential sources. The potential source regions for most source sectors were identified south or southwest of the sampling sites. Risk assessment suggests potential health risks associated with the inhalation of atmospheric PAHs. On a positive note, health risks from coal combustion, liquid fossil fuel combustion, and petrogenic sources at PPT significantly decreased, directly demonstrating the success of emission control in reducing health impacts. In contrast, the health risk from forest fire-related PAH emissions may play an increasing role in the future due to climate change.