Abstract The increasing production of manure is a challenge for livestock management systems as well as the global environment. Being traditionally, and still dominantly, used as fertilizers, land application of manure could preserve soil fertility and improve soil carbon sequestration. However, manure application also increases nitrous oxide (N2O) emissions that might outweigh the benefits of carbon gains. Here we quantify soil carbon change and greenhouse gas (GHG) emissions from corn production systems in the United States from a life-cycle perspective. We show that utilizing manure can reduce mineral fertilizers use, and therefore avoid GHG emissions that would otherwise occur due to mineral fertilizer production and application. As a result, corn produced under manure has a reduced intensity of GHG emissions (1.5 t CO2e ha−1 or 0.15 t CO2e t−1 corn grain), about 15% less than those under sole mineral fertilizers. Owing to a sizeable amount of avoided emissions counterbalancing N2O, the soil carbon gain derived from manure use can largely contribute to net climate change mitigation. It should be noted that GHG emissions estimation can be largely improved as more robust and recent data become available to better represent spatially specific land management and to integrate ecosystem models with life-cycle model. Future studies are merited to further assess the alternative fate of manure, and expand the system boundary to assess agriculture and livestock sectors holistically.