The primary causes of low sesame production are a lack of high-yielding varieties, an inability to adjust to environmental challenges, and a poor response to enhanced crop management. The potential for improving sesame has been investigated using a variety of breeding approaches, including mutation and recombination breeding; however, these methods have only produced a minor increase in productivity. Recombination and mutant breeding have recently been proposed as novel, cutting-edge approaches to overcome the limitations of conventional breeding practices. This study was conducted to assess the recurrent mutagenesis efficacy of sesame crosses, followed by the isolation and evaluation of superior breeding lines that could be released as varieties in the future. In the F4M4 generation, the populations were grown in a randomized block design (RBD), and the efficacy of recurrent mutagenesis was assessed in terms of variability parameters such as the mean, standard deviation, and coefficient of variation. During the F5M5 generation, the materials were grown in three separate trials in Compact Family Block Design to evaluate the between-family and within-family variations, followed by the isolation of improved breeding lines based on per se performance. The improved breeding lines were further advanced to the F6M6 generation for evaluation in three separate trials in an RBD. In the F6M6 generation, ANOVA, correlation, regression, path coefficient, and Mahalanobis’s D
2 analysis were computed, followed by the construction of selection indices to select superior lines. The results showed the importance of three or four EMS treatment cycles for sesame improvement in the F4M4 generation. Twenty of the top lines based on per se performance (with a selection intensity of 27%) from each category in the F5M5 generation were carried forward to the F6M6 generation. In the F6M6 generation, the top six breeding lines (with a selection intensity of 30%) from each category, for a total of 18 breeding lines, were chosen based on these index scores. These high-yielding micromutant lines could be subsequently released as varieties through multiplication trials with standard checks. After a thorough evaluation, these lines have the potential to replace the current varieties and increase production, productivity, and adoption of sesame in India.