Addressing concerns about future food supply and climate change requires identification of management practices that maximize productivity per unit of land while reducing negative environmental impact. The U.S. Corn Belt accounts for 33% of global maize production of 690 million Mg and includes one of the largest irrigated areas in the world on its western fringe. Intensification during past decades has led to the general notion that yield increases occurred at expense of input-use efficiency and greenhouse (GHG) emissions, but this hypothesis has not been tested. Data on grain yield and management practices were used to assess on-farm input-use efficiency, energy balance and greenhouse gas emissions of high-yield, high-input irrigated maize in Nebraska (USA). Irrigated maize achieved high yield, water-, and fertilizer N-use efficiency, concomitantly, indeed much higher than lower-input rainfed maize. High yields and high input-use efficiency resulted in a large positive energy balance and low GHG per yield unit. Observed variation in energy inputs and GHG emissions across site-years was related to differences in applied irrigation and nitrogen (N) surplus in excess of uptake requirements. Hence, input-use efficiency, energy balance, and reduce GHG emissions can be further improved through more precise management of these energy-dependent inputs. The relationship between yield and fossil-fuel inputs of U.S. maize systems at different levels of intensification is fairly linear up to grain yields of ~80% of yield potential. Thus, energy-use efficiency does not decrease with increasing energy inputs up to that yield level, and we conclude it is possible to reconcile high yields with environmental goals in well managed cropping systems, but it requires investment in agriculture research with explicit emphasis on achieving high yields and input-use efficiency together.