Striga species affect the potential productivity of cereals in sub-Saharian Africa due to the lack of durable Striga-resistance in host crops. This study aimed at inducing the new source of resistance in sorghum using gamma irradiation. Dry seeds of three Sorghum varieties; Grinkan, ICV1049 and Sariaso14 were gamma-irradiated with 200 Gy, 300 Gy, 400 Gy and 500 Gy. Screening strategies involved a 2-year field and greenhouse experiments, where mutant Sorghum families, their parents and resistant control were artificially infected with Striga hermonthica seeds. Field screenings revealed induced genetic variability among them, forty families significantly reduced the number of emerged Striga plants or showed good Sorghum grain yield performance despite the infection by S. hermonthica ecotype from Burkina Faso. The induced putative resistant mutants were identified across the four applied gamma-irradiation doses. Greenhouse experiment confirmed Striga resistance in seven mutant Sorghum families leading to no emergence of Burkina’s S. hermonthica ecotype along with high resistance index (RI) and low Striga damage score. Among them, two mutants SA38M5 and IC47M5 withstood S. hermonthica ecotype from Sudan. The induced mutants will be evaluated for the release to farmers for commercial production. Further studies are ongoing on confirmed mutants to highlight their Striga resistance mechanisms and explore the potential of pyramiding different mechanisms to produce durable resistance to S. hermonthica in sorghum.