Apple fruit ring rot (FRR), caused by Botryosphaeria dothidea, is a worldwide disease that impacts Asian apple production regions. However, no substantial progress has thus far been made towardthe mapping of candidate genes or the development of effective genetic makers. In this five-year study, theresistance of 1,733 F1 hybrids from the cross ‘Jonathan’ · ‘Golden Delicious’ was phenotyped by non-wounding inoculation with four B. dothidea isolates. We first conducted systematic comparison of differentanalytic strategies for bulk segregant analysis by re-sequencing (BSA-Seq) and obtained suitable one foroutbreeding species such as Malus. Forty-six quantitative trait loci (QTL) for resistance/susceptibility to thefour isolates, including one QTL ‘hotspot’ on chromosome 14, were identified via BSA-Seq. Using inte-grated multi-omics strategies including RNA-sequencing, parental re-sequencing, BSA-Seq and meta-analysis of RNA-sequencing, fifty-seven candidate genes and corresponding functional mutations fromthe QTL were predicted. Functional mutations located on the candidate genes were validated using kom-petitive allele-specific PCR in hybrids and Malus germplasm accessions with extremely resistant/susceptiblephenotypes. Ten effective markers for apple ring rot were developed. The results provide an example ofrapid candidate gene mapping for complex traits in outbreeding species.