Susceptibility of sorghum seedlings to infection by Sporisorium sorghi, the fungus causing covered kernel smut (CKS) disease, is limited to the period between the sowing of the seed and emergence of the seedling. Microscopy and PCR diagnosis of 7-day-old infected seedlings detected hyphae of S. sorghi in plumule and mesocotyl tissue but not in coleoptile and radicle tissue. Percent infected seedling plumule and mesocotyl tissue detected by microscopy and PCR corresponded well to field resistance classes for CKS in mature panicles of both sorghums tested with Giza-15 being highly susceptible and hybrid Shandweel-305 being resistant. Bulk extracts of phenolics and antioxidants from seedling plumule and mesocotyl tissues of hybrid Shandweel-305 cv significantly inhibited the in vitro mycelial growth of S. sorghi more than those from Giza-15 cv. Moreover, bulk extracts of plumule and mesocotyl tissue of seedlings grown from seed inoculated with S. sorghi teliospores contained higher phenolic and antioxidant content in the resistant hybrid (Shandweel-305) than the highly susceptible cultivar (Giza-15). Similarly, bulk extracts of plumule and mesocotyl tissue of 7-day-old seedlings grown from seed inoculated with S. sorghi teliospores contained higher phenolic and antioxidant content in the resistant hybrid (Shandweel-305) than the highly susceptible cultivar (Giza-15). Ferulic, isorhamnetin and kaempferol acids were detected only in plumule and mesocotyl tissue of resistant hybrid Shandweel-305, whereas ellagic, fumaric and vanillic acids were detected only in highly susceptible Giza-15 cv. Ferulic acid added to malt dextrose broth medium significantly inhibited in vitro teliospore germination and mycelial growth of S. sorghi, especially when added at the highest concentrations. This research established that the mode of seedling infection of sorghum by S. sorghi is almost exclusively through the plumule and mesocotyl tissue. Within these tissues, the presence of the pathogen can induce host production of phenolics, including the fungitoxic ferulic acid and antioxidants at higher concentrations within the resistant sorghum than in the highly susceptible cultivar.