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Salicylic acid (SA) plays a critical role in plant defense against pathogen invasion. SA‐induced viral defense in plants is distinct from the pathways mediating bacterial and fungal defense and involves a specific pathway mediated by mitochondria; however, the underlying mechanisms remain largely unknown. The SA‐binding activity of the recombinant tomato (Solanum lycopersicum) alpha‐ketoglutarate dehydrogenase (Slα‐kGDH) E2 subunit of the tricarboxylic acid (TCA) cycle was characterized. The biological role of this binding in plant defenses against tobacco mosaic virus (TMV) was further investigated via Slα‐kGDH E2 silencing and transient overexpression in plants. Slα‐kGDH E2 was found to bind SA in two independent assays. SA treatment, as well as Slα‐kGDH E2 silencing, increased resistance to TMV. SA did not further enhance TMV defense in Slα‐kGDH E2‐silenced tomato plants but did reduce TMV susceptibility in Nicotiana benthamiana plants transiently overexpressing Slα‐kGDH E2. Furthermore, Slα‐kGDH E2‐silencing‐induced TMV resistance was fully blocked by bongkrekic acid application and alternative oxidase 1a silencing. These results indicated that binding by Slα‐kGDH E2 of SA acts upstream of and affects the mitochondrial electron transport chain, which plays an important role in basal defense against TMV. The findings of this study help to elucidate the mechanisms of SA‐induced viral defense.