Quantitative trait locus (QTL) mapping often yields associations with dissimilar loci/genes as a consequence of diverse factors. One trait for which very limited agreement between mapping studies has been observed is resistance to white mold in soybean. To explore whether different approaches applied to a single data set could lead to more consistent results, haplotype-trait association and epistasis interaction effects were explored as a complement to a more conventional marker-trait analysis. At least 10 genomic regions were significantly associated with Sclerotinia sclerotiorum resistance in soybean, which have not been previously reported. At a significance level of α = 0.05, haplotype-trait association showed that the most prominent signal originated from a haplotype with 4-SNP (single nucleotide polymorphism) on chromosome 17, and single SNP-trait analysis located a nucleotide polymorphism at position rs34387780 on chromosome 3. All of the peak-SNPs (p-value < 0.05) of each chromosome also appeared in their respective haplotypes. Samples with extreme phenotypes were singled-out for association studies, 25–30% from each end of the phenotypic spectrum appeared in the present investigation to be the most appropriate sample size. Some key genes were identified by epistasis interaction analysis. By combining information on the nearest positional genes indicated that most loci have not been previously reported. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses suggest potential candidate genes underlying callose deposition in the cell wall and mitogen-activated protein kinase (MAPK) signaling pathway-plant, as well as plant-pathogen interaction pathway, were activated. Integration of multi-method genome-wide association study (GWAS) revealed novel genomic regions and promising candidate genes in novel regions, which include Glyma.01g048500, Glyma.03g129100, Glyma.17g072200, and the Dishevelled (Dvl) family of proteins on chromosomes 1, 3, 17, and 20, respectively.