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Major coastal upwelling systems are among the most productive marine ecosystems in the world. They contribute disproportionately to the cycling of carbon and nutrients in the ocean and influence marine biogeochemistry beyond their productive regions. Characterized by intense microbial respiration (both aerobic and anaerobic), major coastal upwelling systems are also hotspots for the production and outgassing of potent greenhouse gases (GHG) such as CO2, N2O, and CH4. Quantifying and understanding these roles in the context of a changing climate is therefore a subject of great interest. Here we provide a short synthesis of the current knowledge of the contributions of major coastal upwelling systems to the cycling of GHG. Despite variations within and among different systems, low-latitude coastal upwelling systems typically act as a net carbon source to the atmosphere, while those at higher latitudes function as weak sinks or remain neutral regarding atmospheric CO2. These systems also significantly contribute to oceanic N2O and CH4 emissions, although the extent of their contribution to the latter remains poorly constrained. We also overview recent and future changes to upwelling systems in the context of a warmer climate and discuss uncertainties and implications for GHG production. Although rapid coastal warming is anticipated in all major coastal upwelling systems, the future changes in upwelling-favorable winds and their implications within the context of increased stratification are uncertain. Finally, we examine the major challenges that impede our ability to accurately predict how major coastal upwelling systems will respond to future climate change, and present recommendations for future research to better capture ongoing changes and disentangle natural and forced variability.