A study was undertaken to understand the ToxA-Tsn1 patho-system in spot blotch pathogen Bipolaris sorokiniana of wheat. The ToxA protein functions as a necrotrophic effector causing cell death leading to leaf necrosis in wheat. Similarly, the gene Tsn1 is a sensitivity gene, whose presence is essential for the ToxA-positive pathogen to cause spot blotch. One hundred ten strains of B. sorokiniana collected in the mega environment 5 (ME5A) and ME4C of India showed that ToxA was harbored by 77 (70%) of 110 isolates, while Tsn1 was present in 81 (36.8%) of 220 wheat cultivars assayed. Seedling inoculation of a sample of 20 host cultivars (eleven carrying Tsn1 and nine carrying tsn1) by ToxA positive isolates, showed that only lines carrying Tsn1 developed necrotic spots surrounded by a chlorotic halo. However, there was no such distinction between Tsn1 and tsn1 carriers, when adult plants were inoculated. Even though the disease symptoms were only manifested in cultivars carrying Tsn1, inspection of the infection process revealed that ToxA positive strains were able to successfully form appressoria, penetrate the leaf and sporulate irrespective of whether the host carried Tsn1 or tsn1. The study suggests that wheat breeding for resistance to spot blotch can be managed through monitoring the aggressive isolates harboring BsToxA gene coupled with the use of wheat genotypes, which lack Tsn1.