Anatomical structure variation in roots and stems of grain sorghum (Sorghum bicolor L. Moench) plants, cultivated in pot experiment during the two successive growing summer seasons of 2014 and 2015 as affected by cultivar susceptibility to acremonium wilt disease, Acremonium strictum infection and arbuscular mycorrhizal fungi (AMF) root colonization as biocontrol agent  were investigated. Root of resistant cultivar (Dorado) has more epidermis and exodermis thickness, diameter of root and pith  as well as average number of xylem arms/ vascular cylinder but less cortex thickness and metaxylem vessel diameter in comparison with those of the susceptible one (Giza 54). Infection of susceptible cultivar plants by A. strictum markedly reduced all tested anatomical measurements of roots and stems compared to uninfected one. Hyphae and spores of A. strictum were observed into metaxylem vessels. Marked disintegration and loosening of some cortex cells, pith and metaxylem vessels. The same trend was observed in ground tissue and vascular bundles of stem. Colonization of roots by AMF considerably increased all tested roots and stems anatomical measurements, except metaxylem vessel diameter compared to untreated control. These results may explain the role of AMF root colonization in inducing defense responses grain sorghum as mycorrhizal fungi plant. Inoculation of grain sorghum cv. (Giza 54) by AMF markedly enhanced plant growth expressed as dry weight of roots and shoot as well as soil rhizosphere dehydrogenase activity whereas, disease incidence was reduced by 65% compared to uninoculated plants.