γ-polyglutamic acid (γ-PGA), as an environmentally sustainable material, is extensive applied in agriculture for enhancing water and fertilizer utilization efficiency, augmenting crop yield, and ameliorating soil conditions. However, the effect of γ-PGA in conjunction with sesame cake fertilizer on the soil environment remains uncertain.The aim of this study is to investigate the effect of γ-PGA on soil nutrients, water use efficiency (WUE) and nitrogen use efficiency (NUE), and maize yield across various levels of sesame cake fertilizer. Additionally, the study seeks to identify the optimal ratio to establish a theoretical and practical foundation for sustainable agricultural development and the promotion of ecological agriculture. Through field experiments, nine treatments were established, comprising three levels of sesame cake fertilizer application rates (B1 = 900 kg/hm
2
for low fertility, B2 = 1100 kg/hm
2
for medium fertility, and B3 = 1300 kg/hm
2
for high fertility) and three levels of γ-PGA application rates (R1 = 200 kg/hm
2
, R2 = 400 kg/hm
2
, and R3 = 600 kg/hm
2
). The results can be outlined as follows: (1) When γ-PGA application rate increased, total nitrogen (TN) exhibited a synergistic effect under B1 treatment, but an antagonistic effect under B2 and B3 treatments. At the 6-leaf stage (V6), 12-leaf stage (V12), and tasseling stage (VT), available phosphorus (AP) exhibited antagonistic effects. However, at the filling stage (R2) and maturity stage (R6), AP in B1 and B2 treatments at various depths underwent partial transformation into a synergistic effect. The levels of available potassium exhibited a notable antagonistic effect, leading to a decrease in harvest index (HI). B2 treatment demonstrated superior results compared to the B1 and B3 treatments, with the highest levels observed under B2R1 treatment; (2) TN content in the 0–40 cm soil layer increased during the filling period, and it was uniformly distributed in the 40–60 cm soil layer. When the soil AP was located in the 0–60 cm soil layer, there was an increase in AP content during the mature period. Following the tasseling period, different treatments exhibited varying patterns of increase in response to the presence of potassium within the 0–60 cm soil layer. Consequently, in cases where the sesame cake fertilizer content is low, the interaction between γ-PGA can compensate for the deficiency of fertilizer, thereby enhancing water and nitrogen utilization efficiency. The optimal fertilization strategy for enhancing soil nutrient distribution, WUE and NUE, and yield is proposed to be the application of 1100 kg/hm
2
sesame cake fertilizer and 200 kg/hm
2
γ-PGA.