Crop yield is limited by water and nitrogen (N) availability. However, in Hexi Corridor of northwestern China, water scarcity and excessive fertilizer N in wheat (Triticum aestivum L.) production causes serious conflicts between water and N supply and crop demand. A field experiment was conducted from 2016 to 2018 to evaluate whether reducing of irrigation and fertilizer N will reduce grain yield of wheat. There were two irrigation quotas (192 and 240 mm) and three fertilizer N rates (135, 180, and 225 kg N ha(-1)). The results showed that reducing irrigation to 192 mm and N rate to 180 kg N ha(-1) reduced water uptake, water uptake efficiency, and N uptake of spring wheat as compared to local practice (i.e., 240 mm irrigation and 225 kg N ha(-1) fertilizer). Whereas, it improved water and N utilization efficiency, and water and N productivity. Consequently, the irrigation and N rate reduced treatment achieved the same quantity of grain yield as local practice. The path analysis showed that interaction effect between irrigation and N fertilization may attributable to the improvement of grain yield with lower irrigation and N rate. The enhanced water and N utilization allows us to conclude that irrigation quota at 192 mm coupled with fertilizer N rate at 180 kg N ha(-1) can be used as an efficient practice for wheat production in arid irrigation areas.