Gray mold caused by Botrytis cinerea poses a severe threat to tomato production. In this study, physiological, biochemical, transcriptomic, and proteomic analyses were integrated to characterize the dynamic responses of tomato ‘Ailsa Craig’ to B. cinerea infection. During B. cinerea infection, peroxidase (POD) activity showed a progressive increase, while catalase (CAT) activity was significantly upregulated at 24 hpi and remained stable through 48 hpi. Malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) contents showed a delayed response, increasing significantly only at 48 hpi, whereas SOD activity exhibited a biphasic pattern. Transcriptome and proteome profiling identified 5824 differentially expressed genes and 124 differentially expressed proteins. Functional enrichment analysis highlighted defense-related pathways, including plant–pathogen interaction, flavonoid biosynthesis, and inositol phosphate metabolism. Notably, the chlorophyll a/b-binding protein SlLhcb13 exhibited post-transcriptional upregulation despite transcriptional suppression. Functional validation demonstrated that overexpression of SlLhcb13 enhanced resistance, whereas silencing increased susceptibility. These findings identify SlLhcb13 as a positive regulator linking photosynthesis to immunity and provide new insights into the defense mechanisms of tomato.