Field experiments were conducted during 2015–16 at the Teaching and Research Farm, Ladoke Akintola University of Technology, Ogbomoso, Nigeria to determine the appropriate weeding regimes and agronomic traits in five selected varieties of sesame. Five weeding regimes: no weeding (control), weeding once (at 3 weeks after planting), two weedings (at 3 and 6 weeks after planting), three weedings (at 3, 6 and 9 weeks after planting) and weed free were imposed on five sesame varieties, namely, NCRI BEN-01M (01M), NCRI BEN-02M (02M), NCRI BEN-03L (03L), E-8 and Exotic-sudan (EX) in a split plot arrangement laid out in randomized complete block design (RCBD) and replicated three times. Weeding regime significantly affected the plant growth parameters, number of pods and seed yield of the sesame varieties. Across the five sesame varieties, uncontrolled weeds led to an average of 49% yield reduction, however, 02 M variety exhibited the least tolerance to weed infestation (60% reduction), while other varieties had almost similar values. Seed yield under treatment of two weedings (350.86 kg/ha) or three weedings (413.41 kg/ha) was comparable to those of weed free (411.28 kg/ha) across the varieties in two years. In conclusion, weeding two times was adequate for optimum seed yield production. Growers can successfully cultivate sesame varieties NCRI BEN-01M, NCRI BEN-03L or E-8.