A high-efficiency mode of high-low seedbed cultivation (HLSC) has been listed as the main agricultural technology to increase land utilization ratio and grain yield in Shandong Province, China.  However, limited information is available on the optimized water and nitrogen management for yield formation, especially the grain-filling process, under HLSC mode.  A three-year field experiment with four nitrogen rates and three irrigation rates of HLSC was conducted to reveal the response of grain-filling parameters, grain weight percentage of spike weight (GPS), spike moisture content (SMC), and winter wheat yield to water and nitrogen rates.  The four nitrogen rates were N1 (360 kg ha^–1 pure N), N2 (300 kg ha^–1 pure N), N3 (240 kg ha^–1 pure N), and N4 (180 kg ha^–1 pure N), respectively, and the three irrigation quotas were W1 (120 mm), W2 (90 mm), and W3 (60 mm), respectively.  Results showed that the determinate growth function generally performed well in simulating the temporal dynamics of grain weight (0.989<R²<0.999, where R² is the determination coefficient).  The occurrence time of maximum filling rate (T_max) and active grain-filling period (AGP) increased with the increase in the water or nitrogen rate, whereas the average grain-filling rate (G_mean) had a decreasing trend.  The final 1,000-grain weight (FTGW) increased and then decreased with the increase in the nitrogen rates and increased with the increase in the irrigation rates.  The GPS and SMC had a highly significant quadratic polynomial relationship with grain weight and days after anthesis.  Nitrogen, irrigation, and year significantly affected the T_max, AGP, G_mean, and FTGW.  Particularly, the AGP and FTGW were insignificantly different between high seedbed (HLSC-H) and low seedbed (HLSC-L) across the water and nitrogen levels.  Moreover, the moderate water and nitrogen supply was more beneficial for grain yield, as well as for spike number and grain number per hectare.  The principal component analysis indicated that combining 240–300 kg N ha^–1 and 90–120 mm irrigation quota could improve grain-filling efficiency and yield for the HLSC-cultivated winter wheat.