The present work reveals the beneficial role of sodium nitroprusside (SNP; NO donor concentration: 50 and 100 µM) in mitigation of water stress accompanied by a reduction in viral disease incidence in tomato plants subjected to deficit irrigation. The plants were grown under two irrigation regimes: well-watered (WW; irrigated after the depletion of 55–60% of available soil water) and water deficit (WD; irrigated after the depletion of 85–90% of available soil water) in two seasons of 2018 and 2019. The results indicated that under water stress conditions, plant growth, chlorophyll, relative water content (RWC), and fruit yield were decreased. Conversely, water stress significantly increased the MDA, proline, soluble sugars, and antioxidant enzymes’ activities. Moreover, it was obvious a negligible increase in the fruit content from NO2 and NO3. Water-deficit stress, however, had a positive impact on reducing the percentage of viral disease (TMV and TYLCV) incidence on tomato plants. Similarly, SNP application in the form of foliar spray significantly reduced the disease incidence, the severity, and the relative concentrations of TMV and TYLCV in tomato plants raised under both WW and WD conditions. The treatment of SNP at 100 µM achieved better results and could be recommended to induce tomato plant tolerance to water stress. Thus, the present work highlights the role of NO (SNP) in the alleviation of water stress in tomato plants and subsequent reduction in viral disease incidence during deficit irrigation.