Groundwater irrigation of cropland is expanding worldwide with poorly known implications for climate change. This study compares experimental measurements of the net global warming impact of a rainfed versus a groundwater‐irrigated corn (maize)–soybean–wheat, no‐till cropping system in the Midwest US, the region that produces the majority of U.S. corn and soybean. Irrigation significantly increased soil organic carbon (C) storage in the upper 25 cm, but not by enough to make up for the CO2‐equivalent (CO2e) costs of fossil fuel power, soil emissions of nitrous oxide (N2O), and degassing of supersaturated CO2 and N2O from the groundwater. A rainfed reference system had a net mitigating effect of −13.9 (±31) g CO2e m−2 year−1, but with irrigation at an average rate for the region, the irrigated system contributed to global warming with net greenhouse gas (GHG) emissions of 27.1 (±32) g CO2e m−2 year−1. Compared to the rainfed system, the irrigated system had 45% more GHG emissions and 7% more C sequestration. The irrigation‐associated increase in soil N2O and fossil fuel emissions contributed 18% and 9%, respectively, to the system's total emissions in an average irrigation year. Groundwater degassing of CO2 and N2O are missing components of previous assessments of the GHG cost of groundwater irrigation; together they were 4% of the irrigated system's total emissions. The irrigated system's net impact normalized by crop yield (GHG intensity) was +0.04 (±0.006) kg CO2e kg−1 yield, close to that of the rainfed system, which was −0.03 (±0.002) kg CO2e kg−1 yield. Thus, the increased crop yield resulting from irrigation can ameliorate overall GHG emissions if intensification by irrigation prevents land conversion emissions elsewhere, although the expansion of irrigation risks depletion of local water resources.