Aiming at unbalanced coordination of irrigation and fertilization of winter wheat in the eastern North China Plain, this study investigated the effect of fertigation on wheat grain yield, grain quality, and water use efficiency (WUE) and nitrogen use efficiency (NUE) in seven irrigation and nitrogen (N) fertilization treatments. Under the field conditions, the traditional irrigation and fertilization method (total N amount of 240 kg ha-1 , application of 90 kg ha-1 at sowing irrigation at jointing and anthesis, with topdressing N of 150 kg ha-1 at jointing) was used as the control (CK). There were six fertigation treatments to compare with CK. For the fertigation treatments, the total amount of N application was set to 180 kg ha-1 and 90 kg ha-1 was applied at sowing and the remaining N fertilizer was applied through fertigation. The fertigation treatments included the combination of three fertigation frequencies (S2: at jointing and anthesis; S3: at jointing, anthesis, and filling; S4: at jointing, booting, anthesis, and filling) and two soil water replenishment depths (M1: 0-10 cm; M2: 0-20 cm). The six treatments were S4M2, S4M1, S3M2, S3M1, S2M2, and S2M1. Compared with CK, three and four irrigations (S3 and S4) maintained higher soil and plant analyzer development value and photosynthetic rate after anthesis. These treatments increased soil water extraction while reducing crop water consumption during the whole growing season, promoted the assimilation and translocation of dry matter into the grain after anthesis, and increased the 1000-grain weight. These fertigation treatments also significantly increased WUE and NUE. At the same time, the high grain protein content and grain protein yield were maintained. Compared with the CK, high wheat yield was maintained by S3M1 (drip irrigation fertilizer at the jointing, anthesis, and filling, and the depth of the moisture replenishment is 10 cm). This fertigation treatment significantly increased yield by 7.6%, WUE by 30%, NUE by 41.4%, and partial factor productivity from applied N by 25.8%; grain yield, grain protein content, and grain protein yield also performed well. Consequently, S3M1 treatment was suggested to be a good practice for reducing irrigation water and N input in the eastern North China Plain. © 2023 Society of Chemical Industry.