Sorghum is widely used for producing food, feed, and biofuel, and it is increasingly grown to produce grains rich in health-promoting antioxidants. The conventional use of grain color as a proxy to indirectly select against or for antioxidants polyphenols in sorghum grain was hampered by the lack of consistency between grain color and the expected antioxidants concentration. Marker-assisted selection built upon significant loci identified through linkage disequilibrium studies showed interesting potential in several plant breeding and animal husbandry programs, and can be used in sorghum breeding for consumer-tailored antioxidant production. The purpose of this work was therefore to conduct genome-wide association study of sorghum grain antioxidants using single nucleotide polymorphisms in a novel diversity panel of Sorghum bicolor landraces and S. bicolor × S. halepense recombinant inbred lines. The recombinant inbred lines outperformed landraces for antioxidant production and contributed novel polymorphism. Antioxidant traits were highly correlated and showed very high broad-sense heritability. The genome-wide association analysis uncovered 96 associations 55 of which were major quantitative trait loci (QTLs) explaining 15 to 31% of the observed antioxidants variability. Eight major QTLs localized in novel chromosomal regions. Twenty-four pleiotropic major effect markers and two novel functional markers (Chr9_1550093, Chr10_50169631) were discovered. A novel pleiotropic major effect marker (Chr1_61095994) explained the highest proportion (R2 = 27-31%) of the variance observed in most traits evaluated in this work, and was in linkage disequilibrium with a hotspot of 19 putative glutathione S-transferase genes conjugating anthocyanins into vacuoles. On chromosome four, a hotspot region was observed involving major effect markers linked with putative MYB-bHLH-WD40 complex genes involved in the biosynthesis of the polyphenol class of flavonoids. The findings in this work are expected to help the scientific community particularly involved in marker assisted breeding for the development of sorghum cultivars with consumer-tailored antioxidants concentration.