Fusarium head blight (FHB) is a fungal disease of wheat that reduces yield and results in accumulation of harmful mycotoxins in grain, most importantly deoxynivalenol (DON). DON acts as a virulence factor in wheat and aids fungal spread within the head. FHB is a challenging disease to control because resistance is quantitative, highly polygenic and is often environmentally labile. Increasing evidence indicates that susceptibility factors exist in host plants that fungal pathogens can exploit to promote their colonisation. Disruption of such targets have the potential to confer robust disease resistance. We have identified an FHB susceptibility factor on the short arm of wheat chromosome 4D (4DS) that promotes the spread of the fungus in the head. Our data reveal that its removal or disruption significantly improves resistance to FHB. We developed markers to detect deletions across 4DS and used them to characterise the deletions present in Chinese Spring 4DS terminal deletion bins (CSTdel). FHB disease experiments of CSTdel lines refined the susceptibility factor to a 31 Mbp interval containing 280 high confidence genes. A gamma irradiated population, of the UK spring wheat cultivar Paragon (henceforth referred to as the ‘Paragon population’), was screened to identify lines containing deletions across the interval. These lines were used in disease experiments to further refine the interval. KASP markers, capable of detecting deletions, were designed across the refined susceptibility factor interval to enable further refinement. The deletion lines identified from the initial Paragon population screen were genotyped using the new markers. This fine scale genotyping allowed the deletions to be precisely characterised and reduced the susceptibility factor interval to 7.2 Mbp, containing 51 genes. The entire Paragon population was rescreened to identify lines containing smaller deletions that were not detected in the initial screen. This material has been planted for perform FHB experiments we expect to refine the interval to a few genes. These genes can then be analysed using Cadenza TILLING mutants. Using the same method, we have also identified and refined the position of a factor that increases resistance to DON. The DON resistance factor is close to the fungal susceptibility factor on 4DS and has been restricted to a 4.2 Mbp interval containing 50 genes.