In common root and crown rot (CRR), Bipolaris sorokiniana (Sace.) is one of the important in wheat, causing considerable yield losses globally. Sources of resistance can provide a feasible and effective method of control for plant disease management. However, knowledge on mechanisms of resistance is scarce.• We screened 33 wheat genotypes against B. sorokiniana under greenhouse and field conditions. In addition, real-time quantitative PCR (qPCR) analysis using ten novel candidate gene markers, Cre3, EDS1, LTP5, PGIP, PR-1, PIEP1, TLP, UGT, Stb6 and PFT, was conducted on leaves and roots, along with changes in activity of antioxidant enzymes, peroxidase, catalase, b-1,3-glucanase, and phenolic content for their involvement in disease impact mechanisms.• Lowest disease severity was in 'Alvand', followed by 'Baharan' and 'Bam' as resistant genotypes. Quantitative gene expression showed that, although the candidate defence genes were upregulated 1.24-to 3.5-fold in wheat roots and leaves inoculated with B. sorokiniana, they were highly regulated in resistant varieties 'Alvand', 'Mehregan' and 'Bam'. Cre3, a resistance gene to cereal cyst nematode Heterodera filipjevi, was regulated in cultivars resistant to B. sorokiniana. Similar results were obtained for Stb6, a gene resistant to Septoria tritici blotch, EDS1 resistant to powdery mildew, Blumeria graminis, and the genes PR-1 and UGT resistant to leaf rust, Puccinia triticina. Antioxidant enzyme activity also showed the highest increases in resistant genotypes.• In conclusion, the T. aestivum-B. sorokiniana interaction in resistant wheat cultivars uses defence-related genes and enzymes that protect wheat towards sustainable development. Further such studies will shed light on simultaneous resistance to other diseases in wheat cultivars.