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 those for Fhb1 and Fhb7, to enhance barley resistance to FHB. TaHRC is a wheat gene that encodes a putative histidine-rich calcium-binding protein and has been identified to be involved in the Fhb1-mediated resistance. BLAST searches indicate that orthologues of TaHRC are 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 transferred Fhb7 encoding a glutathione S-transferase (GST), driven by either the native promoter or a constitutive promoter, into barley cv. Bowman through Agrobacterium-mediated transformation. Homozygous loss-of-function HvHRC mutants and Fhb7-transformants were identified using Sanger sequencing and real-time PCR (q-PCR), respectively. Our preliminary field studies suggested that both the disruption of HvHRC and overexpression of Fhb7 in barley improved resistance to FHB. Therefore, bioengineering cloned genes involved in FHB resistance in wheat may provide novel strategies to reduce impacts of this destructive disease in barley.