Powdery mildew, leaf rust and net blotch are major biotic stresses that affect both the quality and quantity of the yield of barley. The current research was conducted at Sids Research Station during 2016/17 and 2017/18 growing seasons in Egypt. We aimed to identify the quantitative trait loci (QTL) and digenic epistatic interactions controlling the resistance to the aforementioned diseases in a doubled haploid population (S42) of barley derived from the cross between the exotic accession of H. vulgare ssp. spontaneum ‘’ISR42-8’’ and the German spring barley cultivar ‘’Scarlett’’ (H. vulgare ssp. vulgare). Results indicated that the wild parent is more resistant to the investigated diseases than the cultivated barley; in addition, a favorable transgressive segregation was detected for all investigated diseases. The QTL analysis showed that the alleles of the marker bPb-9668 (4H, 145.02 cM) displayed favorable performance of decreasing powdery mildew severity in the S42 population. In addition, three QTL were mapped to 2H, 3H and 5H, which associated with the resistance of leaf rust. The alleles of the three detected QTLs showed favorable performance of decreasing leaf rust severity in the S42 population by values ranging between -33.54 and -17.73 %. The locus QTS.S42.3H that located on chromosome 3H, exhibited both marker main effect and marker × environment interaction. Furthermore, the exotic alleles of this locus exhibited favorable performance of decreasing net blotch severity in the S42 population. Moreover, the epistasis analysis revealed nine desirable pairs of epistatic effects responsible for reducing the severity of the previous mentioned diseases in the S42 population. Our study highlighted that additive × additive epistasis was significant in the inheritance and breeding for the resistance of the investigated barley diseases.