The scarcity of resources has constrained the supply of conventional feedstuffs for livestock production. Consequently, mulberry, known for its high protein and bioactive compounds, has been developed as a promising alternative feed. However, the optimal water-fertilizer ratio for cultivating feed mulberry in the North China Plain and the underlying physiological and agronomic mechanisms remain poorly understood. To address this, a two-year field experiment (2023–2024) was conducted to investigate the effects of water-fertilizer coupling on feed mulberry yield, water use efficiency (WUE), and soil quality. This experiment employed a split-plot design with three irrigation levels (I1=45, I2=90, and I3=135 mm) and four fertilizer rates (F1=0, F2=150, F3=225, and F4=300 kg·ha⁻¹). The results demonstrated that: (1) with variation trends in SWC consistent with those of soil available nitrogen (N), phosphorus (P), and potassium (K) contents. Under water-fertilizer coupling, the total water consumption in the I3F3 treatment reached its peak, increasing by 11.8% and 9.0% compared to I1F1, respectively. (2) Feed mulberry yield increased with elevated irrigation and fertilizer application. The highest yield, along with the peak leaf N, P, and K contents, was achieved under the I3F3 treatment (135 mm irrigation and 225 kg·ha⁻¹ fertilizer). (3) Water and fertilizer use efficiencies exhibited parabolic trends in response to increasing irrigation and fertilizer inputs. The I3F3 treatment emerged as the most effective management strategy, achieving high yield while maintaining superior WUE. However, the highest agronomic nitrogen efficiency (AEN) was observed in I2F2. (4) The AMOS 26 model indicates that water-driven improvement of soil conditions and soil nutrient effects are the key determinants affecting yield; and the content of soil nutrients significantly affects the nitrogen, phosphorus, and potassium contents of the feed mulberry leaves. In summary, feed mulberry exhibits significant potential for providing feed biomass, particularly by maintaining sufficient forage supply during dry seasons. This study provides critical insights for developing efficient water-fertilizer management practices to support China’s intensified animal production systems.