Replacing chemical fertilizers with organic alternatives represents a viable strategy for enhancing agricultural productivity. The optimized integration of both fertilizer types can reduce the chemical input while improving soil conditions. However, the specific impacts of combined organic and inorganic fertilization on soil quality and crop performance require further investigation. To address this, a two-year field experiment was conducted to examine the effects of varying ratios of organic fertilizer substitution on wheat growth, grain yield, nutrient uptake, and soil quality. The results showed that the application of a 100% organic fertilizer combined with a 90% chemical fertilizer significantly increased the wheat biomass and grain yield. In terms of the nutrient uptake efficiency, the aboveground uptake of nitrogen (N), phosphorus (P), and potassium (K) increased significantly by 29.2%, 29.0%, and 56.5%, respectively. The nutrient use efficiency was also improved, with increases of 30.4% for N, 21.1% for P, and 47.7% for K. The partial factor productivity, total nutrient uptake, and the translocation efficiency of N, P, and K were all significantly enhanced. The soil quality was also markedly improved, with increases in both the soil organic matter and nutrient content. In conclusion, substituting chemical fertilizers with organic fertilizers improves the soil moisture and organic matter content, thereby enhancing the total uptake and translocation efficiency of nitrogen, phosphorus, and potassium. This leads to increased nutrient content in wheat grains, resulting in higher yields and improved grain quality. Moreover, this study provides practical guidance for wheat production and supports policy objectives related to sustainable agriculture, reduced chemical fertilizer use, and improved food security.