The agriculture sector has historically been a major source of greenhouse gas (GHG) emissions into the atmosphere. Although the use of synthetic fertilizers is one of the most common widespread agricultural practices, over-fertilization can lead to negative economic and environmental consequences, such as high production costs, depletion of energy resources, and increased GHG emissions. Here, we provide an analysis to understand the evolution of cereal production and consumption of nitrogen (N) fertilizers in Brazil and to correlate N use efficiency (NUE) with economic and environmental losses as N2O emissions. Our results show that the increased consumption of N fertilizers is associated with a large decrease in NUE in recent years. The CO2 eq. of N2O emissions originating from N fertilization for cereal production were approximately 12 times higher in 2011 than in 1970, indicating that the inefficient use of N fertilizers is directly related to environmental losses. The projected N fertilizer forecasts are 2.09 and 2.37 million ton for 2015 and 2023, respectively. An increase of 0.02% per year in the projected NUE was predicted for the same time period. However, decreases in the projected CO2 eq. emissions for future years were not predicted. In a hypothetical scenario, a 2.39% increase in cereal NUE would lead to $ 21 million savings in N fertilizer costs. Thus, increases in NUE rates would lead not only to agronomic and environmental benefits but also to economic improvement. DOI: 10.1371/journal.pone.0135234