Economic or environmental benefits resulting from variable-rate (VR) application of N and seed are uncertain in irrigated maize (Zea mays L.) systems with high yield potential. We evaluated different plant population and N management strategies in two irrigated maize fields in Nebraska. Inputs were varied according to yield zones derived from yield maps, detailed maps of soil organic matter (SOM), and sampled seasonal NO3 status. Uniform management following Best Management Practices (BMPs) resulted in high levels of grain yield (>15 t ha(-1) at Site 1; >12 t ha(-1) at Site 2), nitrogen use efficiency (NUE), and gross return above input cost. Management of high-yielding irrigated systems on relatively flat terrain was not improved through the predictive site-specific approaches tested in this study, which relied on available historical field information (yield maps, weather) and seasonal soil sampling. Among four site-years, only one site-year showed significant increases in yield and NUE and decrease in N input with the VR N. Yield interactions between VR N management strategies and plant population were not significant. More potential for increasing yields, resource efficiency, and profitability may exist through integrating such approaches with dynamic, in-season management of water and N. Such approaches are emerging, but remain to be evaluated thoroughly, particularly under high-yielding conditions and against conventional BMPs.