Global agriculture is challenged to increase soil carbon sequestration and reduce greenhouse gas emissions while providing products for an increasing population. Growing crop production could be achieved through higher yield per hectare (i.e. intensive farming) or more hectares (extensive farming), which however, have different ecological and environmental consequences. Multiple lines of evidence indicate that expanding cropland for additional production may lead to loss of vegetation and soil carbon, and threaten the survival of wildlife. New concerns about the impacts of extensive farming have been raised for the US Corn Belt, one of the world's most productive regions, as cropland has rapidly expanded northwestward unto grasslands and wetlands in recent years. Here we used a process-based ecosystem model to distinguish and quantify how natural drivers as well as intensive and extensive farming practices have altered grain production, soil carbon storage, and agricultural carbon footprint in the US Western Corn Belt since 1980. Compared to the period 1980–2005, we found that cropland expansion more than tripled in the most recent decade (2006–2016), becoming a significant factor contributing to growing grain production. Land use change in this period led to a soil carbon loss of 90.8 ± 14.7 Tg (1 Tg = 1012 g). As a result, grain production in this region shifted from carbon neutral to a carbon loss of 2.3 kg C kg−1 grain produced. The enlarging negative carbon footprint (ΔC/ΔP) indicates the major role that cropland expansion has had on the carbon cost of grain production in this region. Therefore, we should be more cautious to pursue high crop production through agricultural cropland conversion, particularly in those carbon-rich soils.