Nitrogen use efficiency (NUE) is often used to evaluate an agricultural system's relative ability to process nitrogen (N) inputs. However, no universal indicator has simultaneously considered both economic and environmental objectives. We develop Luenberger indicators of NUE that incorporate both economic and environmental objectives to examine spatio-temporal changes in NUE, which we apply to the Upper Mississippi River Basin (UMRB) for the period 2002--2012. We find considerable spatial-temporal variation in NUE, which could be used to inform future agri-environmental policy and conservation targeting decisions in the UMRB. Using this approach could lead to more cost-effective targeting of areas for N reduction in the UMRB.