Drought is one of the major abiotic stresses which negatively affects plant growth and development. The current study evaluated the effects of drought on the growth, physiology, and biochemical attributes of wheat seedlings; and examined the role of foliar application of ZnO nanoparticles in alleviating drought-induced effects. Two wheat cultivars i.e., Anaj-2017 and FSD-2018 were grown in soil-filled pots and were subjected to 100% field capacity (FC) (well watered) and 50% of FC (drought stress). Whilst different treatments of ZnO nanoparticles spray included no spray, water spray, and 50, 100, and 150 ppm ZnO. Results demonstrated that drought caused a significant reduction in seedling fresh and dry weights, photosynthetic pigmentation, and antioxidant activities compared with a well-watered treatment. Nevertheless, the application of 100 and 150 ppm of ZnO nanoparticles effectively ameliorated the negative effects of drought and enhanced the performance of both cultivars under drought. Data revealed a significant increase in fresh and dry weight of shoot and root with the application of ZnO nanoparticles. A substantial increase of 73.68% and 28.51% in chlorophyll "a" and 26.15% and 50.02% in chlorophyll "b" was recorded with the application of 100 ppm of ZnO nanoparticles in Anaj-2017 and FSD-2018, respectively over control (0 ppm). The application of these nanoparticles also triggered the antioxidant defense system and protected the crop from oxidative damage. Averaged across different stress treatments, application of 150 and 100 ppm of ZnO nanoparticles increased the peroxidase activity by 60% and 72% in FSD-2018, and 15% and 23% in Anaj-2017, respectively compared with no spray. FSD-2018 outperformed Anaj-2017 regarding its overall performance under ZnO treatments and drought conditions. In a nutshell, it can be concluded that ZnO nanoparticles ameliorated the negative impacts of drought by improving the growth, physiology, and antioxidant defense of both wheat cultivars.