An ample amount of water and soil nutrients is required for economic wheat production to meet the current food demands. Nitrogen (N) and zinc (Zn) fertigation in soils can produce a substantial wheat yield for a rapidly increasing population and bring a limelight to researchers. The present study was designed to ascertain N and Zn’s synergistic role in wheat growth, yield, and physio-biochemical traits. A pot experiment was laid out under a complete randomized design with four N levels (N1-0, N2-60, N3- 120, and N4-180 kg ha −1), Zn (T1-0, T2-5, T3-10, and T4-15 kg ha −1) with four replications. After the emergence of the plants, N and Zn fertigation was applied in the soil. The growth traits were considerably increased by combined applications as compared to the sole applications of the N and Zn. The photosynthetic pigments were found maximum due to combined applications of N and Zn, which were positively associated with biomass, growth, yield, and wheat grain quality. The combined application also substantially enhances the antioxidant enzyme activities to scavenge the ROS as H 2O 2 and reduce lipid peroxidation to protect the permeability of the biologic membranes. The combined higher applications of N and Zn were more responsive to ionic balance in a shoot by maintaining the Na + for osmotic adjustments, accumulating more Ca 2+ for cellular signaling; but, combined applications resulted in K + reduction. Our present results suggest that appropriate sole or combined applications of N and Zn improve wheat's growth, yield, and antioxidant mechanisms. Previous studies lack sufficient information on N and Zn combined fertigation. We intend to investigate both the sole and combined roles of N and Zn to exploit their potential synergistic effects on wheat.