The ability of various Streptomyces isolates obtained from soil to induce systemic resistance in tomato (Solanum lycopersicum cv. Supra) plant against Tomato mosaic virus (ToMV) was characterized in current study. Importantly, of nine Streptomyces isolates tested herein, the culture fltrate (CF) of one isolate, designated as Streptomyces ovatisporus LC597360, was the most efective. It exhibited 93.9% biocontrol efcacy and induced a signifcant decrease (17.6±0.8%) of symptoms severity compared with infected control plants. These fnding were confrmed using I-ELISA showing that ToMV concentration was signifcantly reduced in plants treated with S. ovatisporus LC597360 CF as compared with plants inoculated with ToMV. Moreover, treatment with CF of S. ovatisporus LC597360 not only increased activity of defense-related enzymes such as ascorbate oxidase, catalase, peroxidase, and polyphenol oxidase, but also induced plant growth promotion. The present study is the frst one that demonstrates the potential of S. ovatisporus LC597360 in biocontrol of ToMV and investigated its antiviral mechanisms.