Water scarcity is a major limiting factor for crop production in North China Plain (NCP), which produces the majority of the country's winter wheat (Triticum aestivum L.). The objective of this three-year field study was to see if and when irrigation one-time in spring improves grain yield and water use efficiency. Four sets of irrigation were established at the 3-leaf visible stage (L3) and the L4, L5, and L6 stages. The spike number, 1,000-grain weight, and water consumption increased progressively when irrigation time was delayed, whereas grain yield, grain number, dry matter, harvest, and WUE grew, then dropped, and peaked at L4. The increased grain number can be attributed to the L4's higher daily water consumption and water consumption percentage than the L3, L5, and L6 at the jointing-anthesis stages. L4 had a shorter cumulative period of soil drought stress (37 days), whereas L3, L5, and L6 had 40, 42, and 43 days, respectively. Furthermore, flag leaf senescence was postponed in L4 with a better post-anthesis leaf area index, photosynthetic rate, chlorophyll content, stronger superoxide dismutase activity, and reduced malondialdehyde concentration. As a result, single irrigation at the 4-leaf visible stage optimized water deficit and consumption before and after anthesis, resulting in higher yield and WUE in the NCP.