Sesame is sensitive to waterlogging, and its growth is devastatingly impacted under excess moisture conditions. Thus, waterlogging tolerance is crucial to alleviate yield constraints, particularly under expected climate change. In this study, 119 diverse sesame genotypes were screened for their tolerance to 12, 24, 48, and 72 h of waterlogging relative to non-waterlogged conditions. All plants died under 72 h of waterlogging, while 13.45%, 31.93%, and 45.38% of genotypes survived at 48, 24, and 12 h, respectively. Based on the seedling parameters and waterlogging tolerance coefficients, genotypes BD-7008 and BD-6985 exhibited the highest tolerance to waterlogging, while BD-6996 and JP-01811 were the most sensitive ones. The responses of these four genotypes to waterlogged conditions were assessed at different plant growth stages—30, 40, and 50 days after sowing (DAS)—versus normal conditions. Waterlogging, particularly when it occurred within 30 DAS, destructively affected the physiological and morphological characteristics, which was reflected in the growth and yield attributes. Genotype BD-7008, followed by BD-6985, exhibited the highest chlorophyll and proline contents as well as enzymatic antioxidant activities, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). These biochemical and physiological adjustments ameliorated the adverse effects of waterlogging, resulting in higher yields for both genotypes. Conversely, JP-01811 presented the lowest chlorophyll and proline contents as well as enzymatic antioxidant activities, resulting in the poorest growth and seed yield.