Sesame (Sesame indicum L.) is being infected with various pathogens which cause severe losses in oil and seed production. This work aimed to identify the most tolerant cultivars to Fusarium oxysporum f. sp. sesami (Zap) Cast and Macrophomina phaseolina (Tassi) Goid, screening of cultivars for agronomic traits and study the path-analysis of yield and its components. Eight cultivars were evaluated in the field and in the green house under artificial infection of both pathogens for the seasons of 2018 and 2019. The combined analysis revealed significant differences among cultivars for most traits. Int 688 was the best cultivar in seed yield/plant (SY/P) under the infection of the two pathogens. The highest correlations were among SY/P, number of seeds/capsule (NS/C), 1000sw and number of capsules/plant (NC/P) at the genotypic level. Generally, the results of path analysis indicated that both of NS/C and NC/P showed the highest direct and indirect effect on SY/P under the infection both pathogens. It could be concluded that restricted selection by NC/P and NS/C in the segregating generations of crosses among the tolerant parents from these materials could improve seed yield. The reaction of the eight cultivars to the two pathogens in the green house indicated highly significant differences of susceptibility and resistance to Fusarium wilt and charcoal rot among the tested cultivars. Results indicated that Shandaweel 3, Int 688 and Giza 24 cultivars proved to be the most resistant cultivars; they produce the lowest percentages of disease severity of Fusarium wilt and Macrophomina damping-off and charcoal rot.