Frogeye leaf spot is a yield-reducing disease of soybean. To help identify frogeye leaf spot resistance genes, an image-based phenotyping platform was developed. Testing indicated the method is precise and improves upon previously used procedures to phenotype the disease. Soybean breeders have few frogeye leaf spot resistance genes available. To discover new quantitative trait loci (QTLs), a genome-wide association study was conducted with 329 soybean accessions. Eight novel loci were found, including a major QTL on chromosome 11. The marker GSM990 targets a missense mutation at the chromosome 11 locus and was highly associated with resistance. Rcs2 confers resistance to frogeye leaf spot, but the genetic locus has never been mapped. Using a bulked segregant analysis in an F2:3 population, putative loci were identified on chromosomes 11 and 16. Composite interval mapping in the F2:3 population and a RIL population confirmed that Rcs2 is on chromosome 11. Evaluation of recombinant inbred lines narrowed down the QTL to 336 kb. The markers reported can be used to select Rcs2 in soybean breeding. Rcs3 provides strong resistance to frogeye leaf spot. To help uncover the genetic control of Rcs3, the QTL was mapped to a 1.15 Mb region on chromosome 16 in a Forrest × Davis recombinant inbred line population and confirmed by tracing Rcs3 in Davis’s descendants. High-density marker data showed that Davis has a similar haplotype to the cultivars Ralsoy and Arksoy in its pedigree, although phenotyping revealed that they are susceptible to the disease. It was hypothesized that Rcs3 arose as a mutation in Davis or its parent. Tightly linked markers reported can be used for marker-assisted selection. Increasing protein content and improving oil composition are two important but previously distinct goals of soybean breeding. To stack high protein with high oleic and low linolenic acids, two phases of maker-assisted selection were used to select recombinants and stack five loci in three genetic backgrounds. Evaluation of 46 lines in six environments indicated no negative interactions among the traits. Data from four environments suggests that selecting high-yielding cultivars with high protein, high oleic acid, and low linolenic acid is achievable.