Safflower is a conspicuous energy crop might be used as a biofuel and raw material source for vegetable oil and animal feed sectors. It has a potential to reduce energy and oil dependency of Turkey reached to a high level due to its capacity. Weeds can cause yield loss because they compete with the crop for water, light, space, and nutrients in safflower. Weed control practices, therefore, should be made efficiently to gain high safflower yield. The aim of this study is to determine the efficacy of pendimethalin, s-metolachlor, and chlorsulfuron to control weeds and the response of safflower to them. The field experiments were conducted during 2017-2019 in Gölbaşı, Ankara, Turkey. Pendimethalin and s-metolachlor were applied to the soil surface before crop sowing at 675.0, 1012.5, 1350 and 2700, and 686.25, 915.0, 1372.5 and 2745.0 g active ingredient (ai) ha-1, respectively. Chlorsulfuron was treated at 3.75, 4.95, 5.625, 7.5 and 15.0 g ai ha-1 to the weeds when they were 2-4 true leaf stage. Responses of safflower to the herbicides and the efficacy of these herbicides on the weed were visually evaluated 14 and 28 days after treatment (DAT) and before the harvest. Pendimethalin caused very slight crop injury, and the symptoms were disappeared at 28 DAT in 2017, but same symptoms were not observed in 2018. The crop injury caused by chlorsulfuron was transient when it was applied lower than at 5.625 g ai ha-1; however, chlorsulfuron at 7.5 and 15 g ai ha-1 injured persistently safflower plants. Pendimethalin provided moderate control on wild mustard and redroot pigweed at 1350 g ai ha-1 while s-metolachlor at 1372.5 g ai ha-1 sufficiently controlled redroot pigweeds, but not wild mustard. Weed control with chlorsulfuron at higher than 4.95 g ai ha-1 was good compared to lower rates.