The shortage of water resources and the irrational application of nitrogen fertilizer restrict the synergistic enhancement of yield and water- and fertilizer-use efficiencies of wheat in the Huang-Huai-Hai region. In this study, we conducted an experiment following two-factor split zone design with three irrigation levels and four nitrogen application rates. The relative water content of the 0-40 cm soil layer was supplemented to 65% (W 1 ), 75% (W 2 ), and 85% (W 3 ) of field water capacity at the jointing and anthesis stages of wheat. The rates of nitrogen application were 0 (N 0 ), 150 (N 1 ), 180 (N 2 ), and 210 (N 3 ) kg·hm -2 . We analyzed the effects of these different managements on post-anthesis photosynthetic matter production, yield, and water- and nitrogen-use efficiencies. The results showed that yield first increased with increases in the levels of irrigation and nitrogen application, peaking under the W 2 N 2 treatment (9103.53 kg·hm -2 ). However, further increases in water and nitrogen input did not have further enhancement of wheat yield. Under the same nitrogen application condition, compared with W 1 treatment, the canopy light interception rate, chlorophyll relative content and actual photochemical efficiency after anthesis increased by 4.5%-6.0%, 19.7%-28.2%, and 7.5%-9.8% in response to the W 2 treatment, respectively, without any difference between the W 2 and W 3 irrigation levels. At the same irrigation level, post-anthesis dry matter accumulation in repose to the N 2 treatment increased by 80.1%-88.9% and 16.7%-22.2% compared with N 0 and N 1 treatments, respectively, without significant difference between the N 2 and N 3 treatments. Both the irrigation water-use efficiency (IWUE) and the nitrogen partial factor productivity declined with increases in the levels of irrigation and nitrogen application. Under the W 1 , W 2 , and W 3 treatments, the values obtained for IWUE were 16.23, 11.01, and 7.91 kg·hm -2 ·m -3 , respectively, whereas in response to the N 1 , N 2 , and N 3 treatments, N partial factor productivity was 50.8%, 48.4%, and 42.5%, respectively. In all, based on soil moisture measurements and assessments of wheat yield and water- and nitrogen-use efficiencies, the optimal water and nitrogen management strategy for enhancing wheat yield in the Huang-Huai-Hai region is supplementation of water content of 0-40 cm soil layer at the jointing and anthesis stages to 75% field capacity combined with the application of 180 kg·hm -2 nitrogen (W 2 N 2 ). This approach could achieve high yield and efficiency and promote conservation of water and fertilizer.