The root rot/stem "rot/charcoal rot" disease caused by Macrophomina phaseolina (Tassi.) Goid is one of the most destructive disease in all sesame growing areas. To improve tolerance and/or resistance of sesame to this pathogen, two cycles of pedigree selection under artificial infection of were done at Fac. Agric. Assiut Univ. Expr. Farm. Assiut, Egypt. The genetic materials were the F2, F3 and F4 generations of two populations. The experiments were done in the three successive seasons of 2018 to 2020. The F2 was sown in nor-replicated experiments, and the F3 and F4 were raised in RCBD of three replications. The selection criteria were days to 50% flowering (earliness), plant height (PH), height to first capsule (HFC), length of fruiting zone (LFZ) and seed yield/plant (SY/P). The infection % in the F2 ranged from 53.67 to 80.43%. The remained genotypic coefficient of variation in the F4 was high and enough for further cycles of selection for HFC, LFZ and SY/P. Heritability in broad sense of the selection criteria in the F4-generation was very high and unreliable. However, the narrow sense heritability was low to moderate. After two cycles of selection, the direct observed genetic gain from the mid-parent was significant (p ≤ 0.01) and reached -6.06 and -12.15% for earliness,14.66 and 5.82% for PH, 32.35% and 19.19% for LFZ and 43.89 and 36.67% for SY/P for pop1 and pop2, respectively. The infection% decreased significantly by selection. Single trait selection was an effective method to improve the selection criterion, but in some cases, it was accompanied with adverse effects on the other correlated traits. To overcome this problem selection index combined the favorable traits could be recommended.