South America is a large continent situated mostly in the Southern Hemisphere (SH) with complex topography and diverse emissions sources. However, the atmospheric chemistry of this region has been historically understudied. Here, we employ the Multi-Scale Infrastructure for Chemistry and Aerosols, a novel global circulation model with regional refinement capabilities and full chemistry, to explore the sources and distribution of the carbon monoxide (CO) tropospheric column in South America during 2019, and also to assess the effect that South American primary emissions have over the rest of the world. Most of the CO over South America can be explained either by NMVOC secondary chemical production or by biomass burning emissions, with biomass burning as the main explanation for the variability in CO. Biomass burning in Central Africa is a relevant contributor to CO in all of the continent, including the southern tip. Biogenic emissions play a dual role in CO concentrations: they provide volatile organic compounds that contribute to the secondary CO production, but they also destroy OH, which limits the chemical production and destruction of CO. As a net effect, the lifetime of CO is extended to ~120 days on average over the Amazon, while still being in the range of 30-60 days in the rest of South America.