A field experiment was conducted during rainy (Kharif) seasons of 2019 and 2020 to assess the efficacy of the sequential application of pre- and post-emergence herbicides for managing complex weed flora in line sown sesame (Sesamum indicum L.) at Agriculture Research Sub-Station, Sumerpur, Pali. There were nine weed control treatments replicated thrice in a randomized complete block design. Hand weeding twice recorded the highest values of growth parameters and seed yield (1.25 t/ha) which was at par with pre-emergence application (PE) of pendimethalin 750 g/ha followed by (fb) quizalofop-p-ethyl 40 g/ha at 20 days after seeding (DAS). The uncontrolled weeds in weedy check caused 50% sesame seed yield reduction. The post-emergence application (PoE) of quizalofop-p-ethyl 40 g/ha at 20 DAS and sequential application of pre-emergence application (PE) of pendimethalin 750 g/ha PE followed by (fb) quizalofop-p-ethyl 40 g/ha at 20 DAS recorded the highest weed control efficiency, sesame seed yield, net return and benefit cost ratio and were observed to be superior than the recommended practice of pendimethalin 1000 g/ha PE fb hand weeding at 25 DAS.