The combination of organic manure and inorganic fertilizer plays a role in increasing crop yield and nutrient efficiency, but such effectiveness varies with crop, soil, management, and climate. Here, a 6−year field experiment was conducted to evaluate the effects of substituting organic manure with inorganic fertilizer on crop yield, grain protein content, and nitrogen and phosphorus efficiency under a winter wheat−summer maize cropping system on Anthrosol. Five treatments were included: recommended nitrogen (N), phosphorus (P) and potassium (K) fertilizers (NPK), 75%NPK + 25% organic manure (M), 50%NPK + 50%M, 25%NPK + 75%M, and 100%M, respectively. Wheat, maize, and annual yield were 1643–8438 kg ha−1, 4847–11104 kg ha−1, and 10007–17496 kg ha−1. Organic manure treatments produced the same crop yield as NPK treatment except for 100%M. Grain protein content of wheat and maize was 7.9–15.1% and 5.6–12.6%. Organic manure treatments yielded significantly lower wheat grain protein content but had no significant effect on maize grain protein content relative to NPK treatment. Nitrogen uptake efficiency and nitrogen use efficiency at the cropping system level were 0.67–1.16 and 35.7–60.5 kg kg−1. Phosphorus uptake efficiency and phosphorus use efficiency were 0.28–0.75 and 167–531 kg kg−1. Compared with NPK treatment, 50%M, 75%M, and 100%M improved nitrogen use efficiency but decreased nitrogen uptake efficiency and phosphorus efficiencies. Annual N and P budgets were −1.3–79.1 kg ha−1 a−1 and 25.6–100.1 kg ha−1a−1, and both increased with the increase in organic manure input. Based on crop yield, grain protein content, nitrogen, and phosphorus efficiency and their budget, substitution of 25% inorganic fertilizer with organic manure is the rational combination under the winter wheat–summer maize system on an Anthrosol.
