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 H2O2 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 Ca2+ 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.