The effects of combined application of organic fertilizer and chemical fertilizer on yield, quality, and water use efficiency of dryland wheat were studied, which provided theoretical basis for substituting chemical fertilizer with organic fertilizer and reducing annual yield fluctuation in dryland wheat field in loess hilly region. In 2017—2019, the effects of constant chemical fertilizer (B), constant chemical fertilizer substituted by pig manure (A₁B₁, substituted by 20%; A₁B₂, substituted by 30%; A₁B₃, substituted by 40%) and constant chemical fertilizer substituted by sheep manure (A₂B₁, substituted by 20%; A₂B₂, substituted by 30%; A₂B₃, substituted by 40%) on the yield and composition, grain nutritional quality, flour processing quality, and water use efficiency of dryland wheat were studied. The results showed that, compared with the application of chemical fertilizer only, the combined application of organic fertilizer and chemical fertilizer can improve the yield, grain bulk density, hardness index, protein content, and flour sedimentation value of dryland wheat, and chemical fertilizer substituted by proper amount of organic fertilizer can increase water use efficiency. The effects of pig manure and sheep manure on yield and water use efficiency were different under different years. Compared with sheep manure combined with chemical fertilizer, the spike number and kernels per spike of dryland wheat were increased and the yield and water use efficiency were improved by pig manure combined with chemical fertilizer in wet year, which showed periodic drought in growth period and freezing injury in spring. Compared with pig manure combined with chemical fertilizer, the spike number, yield, and water use efficiency were increased by sheep manure combined with chemical fertilizer in dry years that had precipitation in key growth period and high water storage in fallow period. The proportion of organic fertilizer substituting for constant chemical fertilizer varies with the type of organic fertilizer. Pig manure substitute for 20% chemical fertilizer was the best, increased yield by 39.76% and 2.46% compared with the application of chemical fertilizer only respectively, and increased water use efficiency by 4.91 kg/(hm²·mm) in 2018; sheep manure substitute for 40% chemical fertilizer was the best, increased yield by 18.88% and 2.28% compared with the application of chemical fertilizer only, and increased water use efficiency by 2.57 kg/(hm²·mm) and 12.68 kg/(hm²·mm) respectively. In the two extreme years’ experiment, the reduction of chemical fertilizer combined with pig manure or sheep manure could improve wheat yield and water use efficiency, improve wheat quality, and increase soil organic matter content in topsoil. Considering from the dour qualities and the point of fertilizer saving, 20% chemical fertilizer that substituted by pig manure or 40% substituted by sheep manure is recommended for the wheat production in Southern Shanxi Province.