Abstract The changing composition of the atmosphere, driven by anthropogenic emissions, is the cause of anthropogenic climate change as well as deteriorating air quality. Emission inventories are essential to understand the contribution of various human activities, model and predict the changing atmospheric composition, and design cost-effective mitigation measures. At present, national emission inventories in South America (SA) focus on Greenhouse Gases (GHG) as part of their obligation to the United Nations Framework Convention for Climate Change (UNFCC) within the framework of their national communications. Emission inventories other than GHG in SA focus mainly on growing urban areas and megacities. Therefore, studies examining air quality at national, regional or continental scales in SA depend on (down-scaled) global emission inventories. This paper examines the emission estimates of air pollutants from various global inventories for five SA countries, namely Argentina, Brazil, Chile, Colombia and Peru. A more detailed analysis is conducted for the EDGAR and ECLIPSE emission inventories, in particular comparing local city-scale inventories of a major city in each country. Although total emissions between down-scaled global inventories and local city inventories are often comparable, large discrepancies exist between the sectoral contributions. This is critical, as the mitigation of poor air quality will depend on addressing the right sources. Potential sources of discrepancies between global and local inventories include the spatial distribution proxies, difference in emission factors used and/or the use of generic statistical country data when estimating emissions. This highlights the importance of using local information when generating national emission inventories, especially for air quality modeling and development of effective mitigation measures. This study represents the first step towards an increased understanding of the strengths and weaknesses of emissions information in SA.