Developing a high yielding variety connected with stress-resistant in sesame is a viable option to address the adverse effects of climate change. The objectives of this study were to identify high-yielding and to detect some molecular markers associated with Fusarium wilt resistance in sesame. Five genotypes were evaluated based on seed yield ha-1 over three growing seasons (2016-2018) at two sites, Al-Nubaria (2016-2018) and AbuHammad (2016) in Egypt. Twenty RAPD and five ISSR primers used to detect some markers linked to Fusarium wilt resistance. Genotypes and environments and interaction between them showed high significant variation (p<0.05) for seed yield ha-1. The mean performance of the lines C1.5, C3.8, C6.3, and C1.6, for seed yield ha-1 were higher than check variety by 3.4, 2.8, 0.5 and, 16.7%. Line C1.6 achieved less value of the standard deviation of ranks, based on seed yield ha-1, through environments, indicating that it was less affected by environmental conditions. Molecular marker analysis revealed eight markers linked to Fusarium wilt resistance, they are seven positive markers (five RAPD and two ISSR) which were found in the line C3.8 and absent in the check variety. Finally, both C1.6 and C3.8 offering prospects to form new varieties sesame having high-yield and Fusarium wilt disease resistance.