The eco-efficiency index (EEI) framework has been used to determine economically and environmentally optimal nitrogen (N) fertilizer application rates for some pollutants (such as greenhouse gas emissions) for selected agricultural production systems. However, previous EEI applications have not examined N application rates linked to nitrate-N loss from crop production. The research gap is surprising given the importance of nutrient N in crop production and concerns with nitrate-N in groundwater systems. Eco-efficiency of crop production systems are increased for farm management practices which generate higher economic returns and lower negative environmental impacts and, therefore are considered more eco-efficient. Data for the analysis were generated using the SWAT biophysical simulation modeling. The cropping systems evaluated in this study included: i) corn-based cropping systems involving corn-corn-alfalfa-alfalfa-alfalfa (CCAAA), and CCCAA rotations; ii) potato-based cropping systems involving potato-corn-barley-potato-corn (PCBPC) and PBWPC; and iii) vegetable-horticulture cropping system involving potato-winter wheat-potato-carrot-corn (PWRC) all managed under conventional tillage (CT) and no-till (NT) systems. Estimated eco-efficient N fertilizer rates were substantially lower than current NMP-recommended rates (NMP N rates) and the maximum economic rate nitrogen fertilization (MERN). However, the actual amounts depended on the crop and rotation system. CCAAA-CT was the most eco-efficient rotation choice among the corn-based cropping systems considered. Similarly, PCBPC-CT was the most eco-efficient choice among the potato-based production systems. In addition, when the NMP-recommended N rate was replaced by the EE N rate for the vegetable horticulture cropping system, the eco-efficient cropping system shifted from a rotation involving CT to a NT system. Eco-efficient N fertilization rates that explicitly simultaneously considers economic and environmental dimensions of cropping system performance will require substantial trade-offs between farm returns and reduction in nitrate pollution.