Wheat is an important global staple food crop; however, its productivity is severely hampered by changing climate. Erratic rain patterns cause terminal drought stress, which affect reproductive development and crop yield. This study investigates the potential and zinc (Zn) and silicon (Si) to ameliorate terminal drought stress in wheat and associated mechanisms. Two different drought stress levels, i.e., control [80% water holding capacity (WHC) was maintained] and terminal drought stress (40% WHC maintained from BBCH growth stage 49 to 83) combined with five foliar-applied Zn-Si combinations (i.e., control, water spray, 4 mM Zn, 40 mM Si, 4 mM Zn + 40 mM Si applied 7 days after the initiation of drought stress). Results revealed that application of Zn and Si improved chlorophyll and relative water contents under well-watered conditions and terminal drought stress. Foliar application of Si and Zn had significant effect on antioxidant defense mechanism, proline and soluble protein, which showed that application of Si and Zn ameliorated the effects of terminal drought stress mainly by regulating antioxidant defense mechanism, and production of proline and soluble proteins. Combined application of Zn and Si resulted in the highest improvement in growth and antioxidant defense. The application of Zn and Si improved yield and related traits, both under well-watered conditions and terminal drought stress. The highest yield and related traits were recorded for combined application of Zn and Si. For grain and biological yield differences among sole and combined Zn-Si application were statistically non-significant (p>0.05). In conclusion, combined application of Zn-Si ameliorated the adverse effects of terminal drought stress by improving yield through regulating antioxidant mechanism and production of proline and soluble proteins. Results provide valuable insights for further cross talk between Zn-Si regulatory pathways to enhance grain biofortification.