Herein, the impact of chitosan fabricated biogenic silver nanoparticles (Ch@BSNP) has been evaluated for the protective management of bacterial leaf spot (BLS) disease in tomatoes caused by Xanthomonas campestris (NCIM5028). The Ch@BSNP originated by the Trichoderma viride (MTCC5661) derived extracellular compounds and subsequent chitosan hybridization. Spherical-shaped Ch@BSNP (30–35 nm) treated diseased plants were able to combat the biotic stress, as evidenced by the decreased elevated response of stress markers viz; anthocyanin (34.02%), proline (45.00%), flavonoids (20.26%), lipid peroxidation (10.00%), guaiacol peroxidase (36.58%), ascorbate peroxidase (41.50%), polyphenol oxidase (25.34%) and phenylalanine ammonia-lyase (2.10 fold) as compared to untreated diseased plants. Increased biochemical content specifically sugar (15.43%), phenolics (49.10%), chlorophyll, and carotenoids were measured in Ch@BSNP-treated diseased plants compared to untreated X. campestris-infested plants. The Ch@BSNP considerably reduced stress by increasing net photosynthetic rate and water use efficiency along with decreased transpiration rate and stomatal conductance in comparison to infected plants. Additionally, the expression of defense-regulatory genes viz; growth responsive (AUX, GH3, SAUR), early defense responsive (WRKYTF22, WRKY33, NOS1), defense responsive (PR1, NHO1, NPR1), hypersensitivity responsive (Pti, RbohD, OXI1) and stress hormones responsive (MYC2, JAR1, ERF1) were found to be upregulated in diseased plants while being significantly downregulated in Ch@BSNP-treated diseased plants. Furthermore, fruits obtained from pathogen-compromised plants treated with Ch@BSNP had higher levels of health-promoting compounds including lycopene and beta-carotene than infected plant fruits. This nano-enabled and environmentally safer crop protection strategy may encourage a sustainable agri-system towards the world's growing food demand and promote food security.