Black root rot (BRR), incited by the soilborne pathogen Thielaviopsis basicola has the potential to cause significant economic loss in cotton (Gossypium spp.) production. Cultivated tetraploids of cotton (G. hirsutum and G. barbadense) are susceptible although resistant types have been identified in a possible tetraploid progenitor, G. herbaceum. Genetic mapping was used to detect the chromosomal locations of quantitative trait loci (QTL) that confer resistance to the BRR pathogen. A population of F2 individuals (G. herbaceum x G. arboreum) and F2:3 progeny families were examined. Phenotypic variation between resistant and susceptible reactions could be explained partly by three QTL. The BRR5.1, BRR9.1, and BRR13.1 QTL each explained 19.1, 10.3 and 8.5% of the total phenotypic variation, respectively. The combination of all three in a single genetic model explained 32.7% of the phenotypic variation. Comparative analysis was conducted on significant QTL regions to deduce the cotton-Arabidopsis synteny relationship and examine the correspondence between BRR QTL and Arabidopsis pathogen defense genes. Totally 20 Arabidopsis synteny segments corresponded within one of three BRR QTL regions. Each synteny segment contains many potential Arabidopsis candidate genes. A total of 624 Arabidopsis genes, including 22 pathogen defense and 36 stress response genes, could be placed within the syntenic regions corresponding to the BRR QTL. Fine mapping is needed to delineate each underlying BRR R-gene and possible Arabidopsis orthologs. Research and breeding activities to examine each QTL and underlying genes in Upland cotton (G. hirsutum) are ongoing.