Water shortages due to low precipitation and seawater intrusion in the Lower China Yellow River Delta have occurred in recent years. Exploiting underground brackish water through well drilling is a potential alternative way to satisfy the demand for agricultural irrigation. However, how to successfully use brackish water for irrigation has become a new problem to solve. A two-year field experiment was conducted in this typical saline-alkaline region to investigate the effects of irrigating with brackish water on the soil water-salt dynamics, and the physiological response of winter wheat to drought-salt stress. The experiment was laid out in a randomized block design with three replications according to the quantity (160 mm and 240 mm) and quality (fresh water and brackish water with a salt concentration of 3 g L-1) of irrigation water: T1 was 240 mm of fresh water, T2 was 160 mm of fresh water, T3 was 80 mm of fresh water and 160 mm of brackish water, and T4 was 80 mm of fresh water and 80 mm of brackish water. The results showed that the soil moisture of T3 was almost the same as T1 after the harvest of winter wheat each year, therefore, irrigating with brackish water can maintain soil moisture while saving fresh water resources. After two years, the soil salinity of each treatment increased by 0.307, 0.406, 0.383, and 0.889 g kg-1, respectively. During the jointing-flowering stage, salt stress has a significant inhibitory effect on photosynthesis; T3 and T4 were lower than T1 and T2 in terms of plant height and dry weight. During the filling stage, because the effect of drought stress is more serious than that of salt stress, the photosynthesis of T3 was greater than that of T2 and T4. For both years, the yield of crops followed the rank order T1 > T3 > T2 > T4. Compared with irrigating with fresh water in T1, T3 changed the second and third irrigation into brackish water, however we did not find that soil salinity increased significantly, and this treatment was able to ensure crop growth during the filling stage. Therefore, the combination of fresh water (80 mm), then brackish water (80 mm), then brackish water (80 mm) is a feasible irrigation strategy in China's Yellow River Delta for winter wheat.