To improve grain yields of winter wheat and water-use efficiency in the water-shortage region of the North China Plain (NCP), field experiments involving three irrigation levels and two types of winter-wheat cultivars (Shijiazhuang 8 and Xifeng 20, with moderate and strongly drought tolerance, respectively) were conducted over three growing seasons with different levels of precipitation. The results showed that irrigation significantly improved the grain yield of both wheat cultivars. The response of grain yield was largest in the dry year, followed by the normal and wet years. Shijiazhuang 8 responded more strongly than Xifeng 20. Compared to aboveground biomass under no irrigation treatment, the aboveground biomass of Shijiazhuang 8 and Xifeng 20 improved by 87.0% and 57.8%, respectively, in a dry year, by 27.2% and 18.3%, respectively, in a normal year, and by 13.7% and 11.7%, respectively, in a humid year when irrigation were applied twice. The total water use (TWU) of the two cultivars also increased upon irrigation. The increase was more pronounced in the dry year than in the normal or humid years. However, there were no significant differences in the TWUs of the two cultivars. The water-use efficiency at grainyield level (WUEy) of Shijiazhuang 8 increased significantly upon irrigation in the dry year, did not change in the normal year, and showed a clear decline in the humid year, while the WUEy of Xifeng 20 was reduced by irrigation in each of the three growing seasons. The harvest index (HI) was not altered by irrigation but it did vary by growing season. The HI of Shijiazhuang 8 was always higher than that of Xifeng 20. A positive correlation was found between both the WUEy and the water-use efficiency at the aboveground-biomass level (WUEbm) and the HI. This suggests that the changes in WUEy as a result of irrigation are mainly due to changes in the WUEbm and that the differences in WUEy between the two cultivars were due to differences in WUEbm and HI. These results suggest the following. (1) The TWUs in the two cultivars were roughly equal, although their levels of drought tolerance differed. (2) A wheat cultivar with moderate drought tolerance is expected to be more suitable for the semi-arid region of the NCP. The variety with strongly drought tolerance was able to keep its biomass high and to maintain grain yield under serious drought stress. (3) In order to both increase grain yield and WUEy, two irrigations in a dry year, one irrigation in a normal year, and no irrigation in a humid year will give optimal results in the studied region.