Cladosporium herbarum is one of the most frequently occurring fungal species, with a worldwide distribution, and is found in almost all man-occupied niches in organic and inorganic matter and as a phytopathogen on certain agricultural crops. The structure of the most abundant glycoprotein from the C. herbarum cell wall, peptidogalactomanann or pGM, was previously elucidated and includes carbohydrates (76%), with mannose, galactose and glucose as its main monosaccharides (52:36:12 molar ratio). pGM was able to strongly induce the expression of defense-related genes and ROS accumulation when in contact with BY2 tobacco cells. Here, using two distinct Nicotiana tabacum cultivars, Xanthi and SR1, we evaluated the ability of C. herbarum pGM to induce SAR-like defense by studying its antiviral activity against Tobacco mosaic virus (TMV) and the induction of SAR markers including PR genes and ROS accumulation. Our results show that pGM induced a strong activation of defense responses in treated plants from both tobacco cultivars, contributing to the impairment of viral infection. Expression levels of the pathogenesis-related genes PR-1a (unknown function), PR-2 (□-1-3 endoglucanase) PR-3 (chitinase), and PR-5 (thaumatin-like protein), the phenylpropanoid pathway gene PAL (phenylalanine ammonia-lyase) and genes involved in plant stress responses and innate immunity, such as LOX1 (lipoxygenase) and NtPrxN1 (peroxidase), were strongly induced until 120 h after pGM spray application. Accumulation of superoxide radicals was also observed in a pGM dose-dependent manner.