A field experiment was conducted at ICAR-Indian Institute of Oilseeds Research, Hyderabad during Rabi season of 2023-24 in a red sandy soil. The objective was to evaluate the effect of sequential application of pre-emergence (PE) and post-emergence (PoE) herbicides on weed management, sesame yield and to identify effective herbicides for weed management, yield preservation, and crop safety. Sesame (Sesamum indicum L.) cv “CUMS 17” was line-sown. Among the herbicides tested, pre-emergence application (PE) of pendimethalin 30% + imazethapyr 2% EC (pre-mix) (pendimethalin + imazethapyr) 750+50 g/ha achieved significantly highest weed control efficiency (WCE) at 60 DAS and sesame yield. The sequential application of pendimethalin 750 g/ha PE followed by (fb) post-emergence application (PoE) of haloxyfop-R-methyl 10.5% w/w EC (haloxyfop-R-methyl) 54 g/ha recorded the next highest yield. Pyroxasulfone 85% w/w WG (pyroxasulfone) 127.5 g/ha PE was statistically at par with above sequential application treatment. Bentazone, metribuzin, fluazifop-p-butyl + fomesafen, and propaquizafop + imazethapyr showed phytotoxicity and resulted in lower sesame yield. The uncontrolled weeds in weedy check limited sesame yield to just 33% of the weed free check. It could be concluded that pendimethalin + imazethapyr 750+50 g/ha PE was superior in terms of attaining higher yield of sesame and effective weed management, while pyroxasulfone PE, haloxyfop-R-methyl, and clethodim PoE demonstrated their potential to use for weed management in sesame.