Abstract: This study aims to explore the effect of variety, irrigation mode, sowing date, sowing amount and nitrogen fertilizer application amount on water use efficiency and quality of wheat, and further clarify the influence of internal and external conditions on wheat water use efficiency and quality, and provide a basis for high water and fertilizer use efficiency. A field experiment of 5 factors and 4 levels was conducted with orthogonal optimization design. The results showed that: (1) the factors affecting water use efficiency followed the order of irrigation mode＞ sowing quantity＞ variety＞ sowing date＞ nitrogen fertilizer application amount, and water use efficiency of only jointing water treatment was higher than that of other treatments; (2) variety was the key factor affecting grain protein content, followed by nitrogen fertilizer application amount and irrigation mode, and the effect of sowing date and sowing amount was not obvious; (3) variety was the main factor affecting wet gluten content, and the wet gluten content of‘Yannong 19’was the highest, wet gluten content increased with the increase of nitrogen fertilizer application amount and irrigation times. The biggest impact factor on water use efficiency was irrigation mode, and variety was the most important factor affecting quality. The results lay a foundation for selecting suitable high water use efficiency pattern.