The germination, seedling vigor, crop establishment and yield of agronomically important crops is negatively affected by soil salinity. The current study aimed to investigate the ability of exogenous fertigation by sodium nitroprusside (SNP) to induce salt tolerance in four high yielding wheat cultivars (Sahar-06, Punjab-11, Millat-11 and Galaxy-13) that differ in their response to salt stress in terms of biomass production, oxidative defense mechanisms and grain yield. Three levels of SNP (0, 0.1 and 0.2 mM) were used for seed soaking. During soaking the seeds were kept in the dark. After soaking for 12 h the seeds were air-dried for 5 h before sowing. Salinity caused a significant reduction in biomass and grain yield, while it increased proline (Pro), ascorbic acid (AsA), hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents. Cultivar Sahar-06 and Galaxy-13 were found more tolerant to salinity based on shoot length root fresh and dry wights, 100 grain weight, decreased MDA and H2O2 accumulation, phenolic and ascorbic acid (AsA) contents, accumulation of proline, activities of SOD, POD and CAT as compared to the other cultivars. Seed priming with SNP was effective in reducing the adverse effects of salt stress induced oxidative stress on plant biomass and grain yield in all the studied wheat cultivars, but maximum amelioration of salt stress tolerance by SNP treatment was found in cv. Sahar-06. The increased salt tolerance in wheat plants by SNP seed priming might be due to the role of NO in improving seed vigor and germination and early establishment of seedlings with better growth. 0.1 mM SNP was found the most effective in improving salt tolerance, as compared to other SNP concentations. Exogenous SNP fertigation increased the activities of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) and the contents of AsA, Pro and total phenolics content (TPC) in the salt stressed wheat plants. Our data indicate that SNP-priming induced salt tolerance by up-regulating the antioxidative defense mechanisms resulting in better biomass production and grain yield.