Apples (Malus domestica Borkh.) are one of the most valued temperate fruit crops around the world. Fire blight, caused by the bacterium Erwinia amylovora, is the most destructive bacterial disease affecting apple production globally. With limited disease management options and most commercial cultivars being susceptible to fire blight, prioritizing host-genetic resistance is critical for sustainable fire blight management. While wild Malus species are valuable sources of fire blight resistance QTLs (Quantitative Trait Loci), biological challenges of long juvenility, high heterozygosity, and linkage drag greatly limit their use. M. sieversii is a prime target species given its cross-compatibility with M. domestica, similar fruit size to domesticated apples and valuable source of resistance to economically important pests and diseases including fire blight. This research aims to investigate the genetic loci controlling fire blight resistance from M. sieversii and identify novel QTLs for use in breeding disease-resistant apple cultivars. During this research, a novel, moderate-effect fire blight resistance QTL (Msv_FB7) was identified from M. sieversii ‘KAZ 95 17-14’ (PI 613959) on linkage group 7. Diagnostic markers were developed for the Msv_FB7 QTL to facilitate marker-assisted selection in breeding programs. To fine-map Msv_FB7, large populations segregating for the Msv_FB7 locus were made with crosses of the fire blight-susceptible cultivar ‘Idared’ and three fire blight-resistant progeny from the original biparental population, GMAL4591. Using diagnostic markers flanking the Msv_FB7 region, recombinant progeny were identified, replicated, inoculated with E. amylovora, and further genotyped, narrowing the QTL region of interest for the identification of candidate R-genes. To improve the efficiency of genetic mapping in perennial crops such as apples, an image-based leaf disc assay was developed to rapidly screen seedlings for fire blight resistance. Resistant and susceptible progeny from an interspecific M. domestica _ M. sieversii population segregating for fire blight resistance was selected with this method for an integrated genomic and transcriptomic bulk segregant analysis. Through this combined approach, we identified a novel QTL on the proximal end of chromosome 8 and distal end of chromosome 3, with candidate genes implicated in defense response pathways. The novel identified QTLs, developed diagnostic markers, and a priori candidate genes from this research offer valuable resources for breeding programs aimed at developing fire blight-resistant apple cultivars, contributing to sustainable production systems in the face of evolving pathogen pressures.