A site-specific N management approach has the potential to manage in-field variability and increase production and economic efficiencies by optimizing the nitrogen (N) inputs. Field studies were conducted to investigate the grain yield and protein responses of hard red winter wheat (Triticum aestivum L.) to several N management strategies across variable landscapes. Nine N treatments consisted of various combinations of N rates, sources and timings were applied at specific stages of crop development. Delta yield, delta protein and net returns were calculated to determine the spatial response to N across the field. Those parameters for each treatment varied spatially across the field. Normalized difference vegetation index and leaf area index could not explain the spatial response to N accurately. Overall, grain yield and protein responses to N strategies were highly dependent on the spatial position in each field; however, predicting the responses in time for deploying N management strategies were only weakly associated with canopy sensor data or soil characteristics.