Fusarium head blight (FHB) caused by the fungal pathogen Fusarium graminearum is one of the most devastating diseases in barley (Hordeum vulgare). However, sources of effective resistance to FHB are very limited in barley germplasm. In the present study, we manipulated and employed host genes from wheat (Triticum aestivum), including Fhb1 and Fhb7, to enhance barley resistance to FHB. BLAST searches revealed that the susceptibility allele (TaHRC) of Fhb1, which encodes a putative histidine-rich calcium-binding protein, is widely conserved in cereal species. Using CRISPR-mediated mutagenesis, we have generated loss-of-function mutations in HvHRC, the barley ortholog of TaHRC. Additionally, we also transferred Fhb7, driven by either the native promoter or a constitutive promoter, into barley cv. Bowman through Agrobacterium-mediated transformation. However, the Fhb7 gene was silenced in most of the transgenic plants carrying when it is constitutively expressed. Homozygous loss-of-function HvHRC mutants and Fhb7-transformants were identified using Sanger sequencing and real-time PCR (q-PCR), respectively, which were challenged with the pathogen and phenotyped under field conditions. Our preliminary results suggest that both the disruption of HvHRC and transformation of Fhb7 into barley improved resistance to FHB. Therefore, bioengineering cloned genes involved in FHB resistance in wheat may provide novel strategies to reduce losses to this destructive disease in barley.