Sesame (Sesamum indicum L.) is a poor competitor with weeds during the first four weeks due to the slow growth of its seedlings. Diuron is a systemic urea herbicide used to control broad-leaf weeds in sesame in different countries. Hence, the objective of this study was to assess the efficacy of diuron and thereby for registration in the country. The study, comprised of 12 treatments of combination of diuron and hand weeding was conducted in 2018 and 2019 cropping season in Western Tigray, Ethiopia. The weed control measures were carried out at 10 and 30 days after seedling emergence (DAE) and the weed counting and weighing of weed biomass were undertaken at 10, 17, 30 and 37 DAE. An average number of 197.03 weeds/m2 were counted before the control measure while weed count decreased to 20.8 weeds/m2 after deploying the control measure. The weed biomass was reduced from 889.66 to 166.66 g/m2 and from 175.33 to 61.33 g/m2 after first and second application of the control measures, respectively. The highest crop injury (10%) at 10 days after treatment (DAT) was observed from the application of diuron WG 650 g/ha two times as well as diuron WP 650 g/ha two times equally. The highest efficacy (92.2%) against Commelina foecunda was obtained from diuron WP 650 g/ha. The ANOVA for sesame grain yield showed significant (P<0.001) difference and the highest yield (669.9 kg/ha) with the application of diuron WP 650 g + hand weeding. Yield losses in sesame ranged between 20- 83% because of weed infestation. The diuron has been registered in Ethiopia to be used as post-emergence herbicide in sesame due to its effective weed control ability. The diuron has been registered in Ethiopia to be used as post-emergence herbicide in sesame due to its effective weed control ability.