Grain sorghum [Sorghum bicolor L. (Moench)]is subjected to infection by certain diseases causing great and substantial damage to the crop. Fusarium stalk rot of sorghum caused by F. moniliforme (J. Sheld) represents the common stalk rot in Egypt and many areas of the world.The tested sorghum cultivars reacted differently to F. moniliforme in the two tested seasons. Giza15 sorghum cv. exhibited the highest percentage of infection and disease index followed by Shandaweel 6. Dourado sorghum cv. exhibited the lowest percentage of infection and disease index in both growing seasons. In vitro, the microelements (copper, zinc, manganese and their mixture) at 2g L^-1 significantly reduced the linear growth of F. moniliforme. Copper and the mixture treatment exhibited the highest toxic effect on the tested pathogen, followed by zinc. Manganese exhibited the lowest toxic effect. Seed treatments with different microelements significantly increased peroxidase activity in sorghum leaves as compared with untreated ones. The highest peroxidase activity was obtained in both sorghum cultivars with the mixture treatment and copper then, zinc treatment. Treatment of sorghum seeds with manganese exhibited the lowest peroxidase activity in both Giza15 and Dourado sorghum cultivars. Chlorophyll a and b concentrations in the leaves of copper- and zinc- treated plants were significantly higher than those of manganese compared with untreated plants (control). In mixture treatments, the interaction between sorghum cultivars and microelements had significant effect on chlorophyll content. Based on the present data, it is recommended to use a mixture of microelements on grain sorghum to control or at least alleviate the infection by F.moniliforme.