Fusarium head blight (FHB), primarily caused by a hemi-biotrophic fungus Fusarium graminearum, is a key disease of small grains. Diseased spikes show symptoms of premature bleaching shortly after infection and have aborted or shriveled seeds, resulting in reduced yields. The fungus also deteriorates quality and safety of the grain due to the production of mycotoxins, especially deoxynivalenol (DON), which can result in grain being rejected at the point of sale. Manipulation of susceptibility factors, the plant genes facilitating disease development, offers a novel and alternative strategy for enhancing FHB resistance in plants. In this study, a major effect susceptibility gene for FHB was identified on the short arm of chromosome 7A (7AS). Nullisomic-tetrasomic lines for homoeologous group-7 of wheat revealed the dosage effect of the gene, with tetrasomic 7A being more susceptible than control Chinese Spring wheat, qualifying it as a genuine susceptibility factor. The gene locus was found to be conserved across chromosome 7A substitution lines of five wheat varieties of diverse origins and a tetraploid Triticum dicoccoides genotype. The susceptibility factor was named as Sf-Fhb-7AS and mapped on chromosome 7AS to a 50 Mb peri-centromeric region between del7AS-3 and del7AS-8. Our results show that deletion of Sf-Fhb-7AS imparts 50-60% type-2 FHB resistance. Seed and pollen irradiation panels have been developed in Chinese Spring and Jagger background to further narrow down the region. Identification and manipulation of Sf-Fhb-7AS will be useful for enhancing genetic resistance against FHB in wheat.