Fusarium head blight (FHB) and spot blotch are two important diseases of barley (Hordeum vulgare) in the Upper Midwest. FHB is caused by Fusarium graminearum which produces deoxynivalenol (DON), a toxin harmful to humans and animals. To characterize the genetic architecture of resistance to FHB and DON accumulation, two wild barley (PI 466423 and W-365) accessions with partial resistance were used as donor parents in advanced backcross populations with six-rowed Minnesota malting barley cultivars. The largest effect quantitative trait locus (QTL) identified in the populations was mapped at or near the photoperiod response gene Ppd-H1, which affects heading date and plant height. This result suggests that the QTL for reduced FHB and DON are a pleiotropic effect of that locus. For over 50 years, spot blotch, caused by Cochliobolus sativus, has been controlled in the Upper Midwest through the deployment of durable resistance derived from the breeding line NDB112. Recently, C. sativus isolates (e.g. ND4008) with virulence for the NDB112 resistance have been reported in the region. PI 466423 is resistant to isolate ND4008; therefore, the Rasmusson/PI 466423 population was used to map QTL for resistance to virulent isolate. Four resistance QTL were identified in chromosomes 1H, 2H, 4H, and 5H. The QTL on chromosomes 1H, 4H, and 5H were contributed by PI 466423, while the one on chromosome 2H was contributed by Rasmusson. A gamma radiation-induced susceptibility mutant from cultivar Morex was used in an RNAseq experiment to study the early infection response of barley to C. sativus. Differential expression analysis between the two genotypes revealed a role for lipid signaling in the resistance response, which may activate the jasmonic acid pathway.