A field experiment was conducted at Shandaweel Research Station, Sohag Governorate during 2012 and 2013 seasons to investigate the influence of three water regimes at 100, 80 and 60% of field capacity, two sesame cultivars ( Shandaweel 3 and Sohag 2000 ) and six weed control treatments (Prometryn at rate of 375 g active ingredient (a. i) /fed. , bentazon at rate of 240 g a. i /fed., prometryn and bentazon with one hand hoeing, hand hoeing twice and weedy check) on water relations and sesame productivity. A split-split plot design with three replications was used. The results showed that irrigating sesame at 60 % of FC significantly reduced annual broad leaved, grassy and total weeds in both seasons compared to irrigation water at 100% of FC. While, irrigation at 100% of FC significantly increased growth and yields of sesame and its attributes compared to irrigation at 60 % FC. Sohag -2000 cultivar significantly inhibits growth of annual broad leaved, grassy and total weeds and increased plant height, number of branches and capsules /plant, capsule length, 1000-seed weight, seed yield and oil %, compared with Shandaweel-3 cultivar. All weed control treatments significantly reduced the dry weight of annual broad leaved, grassy and total weeds in both seasons. Hand hoeing twice, bentazon followed by H.H. once, + prometryn follow by H.H. once, gave the highest reduction % in the total annual weeds and increased significantly plant height, the number of branches / plant, number of capsules /plant, capsule length, 1000 seed weight, seed yield /fad. and oil %, compared to un-weeded treatment. Water consumptive use (CU) values were 2252.6, 2016.1, 1656.9, 2261.7, 2020.4 and 1654.2 m 3 /fed for 100, 80 and 60 % of FC treatment , respectively, in both seasons. The highest value of water use efficiency (WUE) was recorded by irrigation at 80 % of FC. The highest CU and WUE were recorded by Sohag -2000 cultivar, compared to Shandaweel-3 cultivar. Under the conditions of this experiment sowing Sohag-2000 cultivar with using hand hoeing twice, bentazon followed by H.H. once, and prometryn followed by H.H. once and irrigation at 80 % of FC can be recommended to obtain the highest oil and sesame yield/fed.