Fusarium head blight (FHB), a devastating disease of barley caused primarily by the fungus Fusarium graminearum, can cause significant yield losses and grain contamination with mycotoxins. Enhancing genetic resistance to FHB and the resultant accumulation of mycotoxins is one of the most effective and economical methods of reducing losses caused by FHB. Our future objective is to develop a multi-parent advanced generation intercross (MAGIC) population using the most resistant two-rowed barley accessions possessing complementary haplotypes at characterized FHB/DON loci with the goal of identifying progeny with resistance enhanced beyond the level of the founder parents. A panel of 247 diverse barley accessions from world-wide collections previously observed to exhibit promising levels of FHB resistance was evaluated in up to 10 environments over the past six years at two locations in Minnesota. The panel was genotyped using the 50k Infinium iSelect genotyping array for barley and association mapping was performed to identify quantitative trait loci (QTL) controlling FHB severity and deoxynivalenol (DON) concentration. Multiple FHB and DON QTL were detected, notably independent of QTL influencing heading date, plant height, and row type. These significant marker-trait associations were used to generate multi-marker haplotypes in relevant genomic regions. Haplotype-trait associations were then tested using the haplo.stats package in R. A group of 21 two-rowed candidate parents was selected based on FHB and DON phenotypes, as well as key agro-morphological traits including heading date and plant height. The R package PopVar was used to predict genetic variance and superior progeny means for simulated biparental populations for all parental combinations of the 21 selected lines. Utilizing the predicted cross means and variances, as well as the haplotype information for the selected lines, eight parents were selected to serve as the founders for the multi-parent advanced generation intercross (MAGIC) population. Three of the eight founder parents are agronomically advanced lines, which will increase the chances of recovering progeny with desirable agronomic and quality traits beyond resistance to FHB and the accumulation of DON. Over the next three years, additional intercrosses and selfing generations will be performed to generate 800-1000 recombinant inbred lines (RILs) that will be phenotyped for disease reaction and mycotoxin concentration in multiple environments. Progeny carrying novel combinations of alleles from multiple founder parents at key haplotype loci are expected to have enhanced resistance to FHB and DON accumulation.