Septoria tritici blotch (STB), caused by Mycosphaerella graminicola has recently become one of the devastating diseases in Iran causing significant yield losses on most commercial bread and durum wheat cultivars. Iran is located in the Fertile Crescent, a region where wheat was historically domesticated; and, thus, landraces derived from this region are of considerable global interest for identification of new sources of resistance to various stresses. Here, we report on the resistance responses of 45 tetraploid wheat landraces collected from different provinces of Iran to eight M. graminicola isolates. In total 138 isolate-specific resistances were found among all interactions (n=360). The highest number of specific resistances (30 out of 32 interactions) was found in wheat landraces collected from West Azarbaijan. In contrast, all landraces from Kordestan were highly susceptible to M. graminicola isolates and only one isolate-specific resistance was identified among 106 isolate-wheat interactions. Kermanshah landraces showed the highest resistance variation against different isolates. About 57 isolate-specific resistances were identified among 104 interactions. Ilam landraces were highly resistant to STB as 28 specific resistances were observed among 32 interactions. Markazi (n=2) and Sistan-Baluchestan (n=1) were susceptible to all isolates tested. Landraces from Lorestan were generally susceptible to isolates tested as 26 susceptible responses were observed out of 32 interactions. Our results indicate that landraces collected from the Fertile Crescent region may possess diverse effective resistance genes or valuable broad spectrum resistance genes, and that their identification is of interest and can be exploited in breeding programs.