The Septoria Leaf Blotch Complex (SLBC), caused by the two ascomycetes Zymoseptoria tritici and Parastagonospora nodorum, can reduce global yearly yield of wheat by up to 50%. In the last decade in Italy, SLBC incidence has increased; notably, durum wheat has proven to be more susceptible than common wheat. Field fungicide treatment can efficiently control these pathogens, but it leads to the emergence of resistant strains and adversely affects human and animal health, and the environment. Our previous studies indicated that active compounds produced by Trametes versicolor can restrict the growth of mycotoxigenic fungi and the biosynthesis of their secondary metabolites (e.g. mycotoxins). Specifically, we identified Tramesan: a 23 KDa -heteropolysaccharide secreted by T. versicolor that acts as a pro-antioxidant molecule in animal cells, fungi, and plants. Foliar-spraying of Tramesan (3.3 µM) in SLBC-susceptible varieties of durum significantly diminished symptoms of Stagonospora Nodorum Blotch (SNB) and Septoria Tritici Blotch (STB) by 75% and 65%, respectively. Tests were conducted under controlled conditions as well as in field. We show that Tramesan elicits wheat defence against SNB and STB augmenting the synthesis of defence-related hormones, notably JA and SA, that in turn switch on the expression of markers of defence (PR1, PR4 inter alia). In field experiments, yield of durum wheat plants treated with Tramesan was similar to that of untreated ones. The results suggest the use of Tramesan for protecting durum wheat against SLBC.