Abstract. Exploring an effective fertilization practice is crucial for achieving a sustainable dryland winter wheat cropping system. Following a split-plot design, this study was conducted to investigate the combined effect of manure (-M or +M; main plot) and various rates of nitrogen (N) fertilizer (0, 75, 150, 225, and 300 kg N ha-1; sub plot) on grain yield, water and N use efficiencies of winter wheat, and soil nutrients. The results showed that the treatments with manure improved the grain yield by 8%, and WUE by 10% relative to that without manure throughout the study years. The highest winter wheat yield and WUE were both recorded in the M+N225 treatment, which were not significantly different from those for M+N75 and M+N150 treatment. In contrast, high levels of N fertilizer (> 150 kg N ha-1) combined with manure not only caused a reduction in the N use efficiency (NUE), but it also caused an increase in the soil residual nitrate-N (from 43.7 to 188.9 kg ha-1) relative to without manure. After three years of continuous cropping, the treatment combining manure with 150 kg N ha-1 fertilizer had the highest SOM, available P and available K, which was 24%, 379% and 102% higher than that for unfertilized treatment (CK), and 10%, 267%, and 55% higher than that for without manure, respectively. Thus, the combination of manure (17.5 t ha-1 poultry or 30 t ha-1 pig manure) with 75-150 kg N ha-1 N fertilizer is recommended for improving winter wheat yield, water and N use efficiencies, and reducing soil nitrate-N residue as well.