Abstract: Winter wheat is the main crop in the North China Plain, and its growth is affected by weather, varieties, and management measures. Many scholars have conducted extensive research on the mechanism of winter wheat growth, but most of these studies focused on a single factor. Moreover, research was mostly conducted at the regional scale, with few studies being conducted in areas at the same latitude. To investigate the effects of weather, genotype, and water management interaction on winter wheat yield and water use efficiency (WUE), field experiments were conducted at four typical experimental sites (Hengshui, Nanpi, Luancheng and Nandagang) in the Hebei Plain in the 38° north latitude zone from 2018 to 2019. Three winter wheat varieties 'KN2009', 'GY2018' and 'SL02-1' and two water management levels-irrigation and rain-fed treatments-were used at all four sites. The soil water content was measured at 20 cm intervals in the 1.6 m soil profile before sowing and after harvest. Grain yield and yield components were also measured. Weather factors were collected from a nearby weather station 200-500 m from the experimental sites. Under irrigation conditions, grain yield was 6 316.7 kg·hm^-2, 5 204.1 kg·hm^-2, 4 356.5 kg·hm^-2, and 2 597.7 kg·hm^-2, respectively; WUE was 1.62 kg·m^-3, 1.72 kg·m^-3, 1.36 kg·m^-3, and 1.08 kg·m^-3, respectively; irrigation water use efficiency (IWUE) was 1.62 kg·m^-3, 3.20 kg·m^-3, 2.19 kg·m^-3, and 1.02 kg·m^-3, respectively, at Hengshui, Nanpi, Luancheng and Nandagang sites. Under rain-fed conditions, grain yield at Nanpi, Luancheng, Hengshui and Nandagang was 2 644.4 kg·hm^-2, 2 602.8 kg·hm^-2, 2 422.3 kg·hm^-2, and 1 784.3 kg·hm^-2, respectively; WUE was 1.13 kg·m^-3, 1.10 kg·m^-3, 1.18 kg·m^-3, and 1.01 kg·m^-3, respectively. Grain yield differed significantly among the four sites, while no significant difference was noted among varieties. With regard to WUE, trends differed between the irrigation and rain-fed treatments. The WUE of different sites under irrigation conditions differed significantly, while there were no significant differences among varieties. The WUE of different sites under rain-fed conditions did not differ significantly, while WUE differed to some extent among varieties. Statistical analysis of results for grain yield and yield components revealed that the number of spikes was the most important factor affecting yield, while the effects of grain number per spike and 1000-grain weight on yield were inconsistent with different sites, varieties, and water conditions. Multivariate analysis of variance revealed that the interaction of weather factors and water management had a highly significant effect on yield and WUE (P < 0.01), while weather factors, genotype, and water management had a significant effect on WUE (P < 0.05). Thus, the effects of climate conditions and management measures on winter wheat yield, water consumption, and WUE were significantly greater than those of variety, and water factor was the influential factor on yield and WUE. Based on comprehensive yield, water consumption, and WUE analysis, Nanpi had relatively high grain yield with low water consumption and relatively high WUE. Wheat varieties with strong tillering ability were potentially suitable for planting in this region.