Water for irrigation is a major constraint in the Great Plains, and it is expected that the proportion of irrigated crop land to grow irrigated wheat (Triticum aestivum L.), which requires less water than other crops, will increase to conserve irrigation water. 'NI04421' (Reg. No. CV-1064, PI 659690) hard red winter wheat (Triticum aestivum L.) was developed cooperatively by the Nebraska Agricultural Experiment Station and the USDA-ARS and released in 2010 by the developing institutions and the Wyoming Agricultural Experiment Station. NI04421 was released primarily for its superior performance under irrigation and rainfed conditions in western Nebraska and eastern Wyoming. NI04421 was selected from the cross NE96644/Wahoo (sib) where the pedigree of NE96644 is 'Odesskaya P'/'Cody'//'Pavon 76'/*3 'Scout 66'. The cross was made in the spring of 1998. NI04421 was selected using a modified bulk-breeding method as an F3:4 line (F3-derived line in the F4 generation) in 2002, and in 2004 was assigned experimental line number NI04421. After extensive testing, it was released in July 2010.