Biomass burning is a major source of atmospheric trace gases and aerosols, and Amazonian fires are among its most intense sources globally, with documented impacts on the carbon cycle and regional climate. Long-range transport of Amazonian smoke toward Andean and coastal cities has been reported in individual case studies, but its continental-scale atmospheric footprint, and how it translates into population exposure and health outcomes across South America, remains poorly quantified. Here, we address this gap by combining Lagrangian plume tracking, regional chemical transport modeling (WRF-Chem), satellite fire data, and health-impact functions to characterize how Amazonian burning perturbs atmospheric composition across the continent and how that perturbation drives population exposure in major South American cities. We show that Amazonian burning generates a recurrent, continental-scale smoke season during the austral dry season (June–November), with transport corridors carrying fire-derived PM_2.5 to cities along the Andes, the Pacific coast, southeastern Brazil, and the southern cone. This atmospheric perturbation is substantial: WRF-Chem simulations indicate 50–100 μg/m³ of added PM_2.5 across the basin during peak months, translating into an estimated 33,000 (CI:19,700–48,900) excess premature deaths annually across South America. Fire trends reveal strong geographic contrasts linked to land-use dynamics and governance, and countries that have already curbed Amazonian fires show that the tools to reduce this burden exist wherever political will meets social awareness. As climate change reshapes fire regimes and these transport corridors, whether governance and mitigation efforts can keep pace with the resulting burden remains an urgent open question.