Glyphosate-resistant (GR) weeds are the biggest concern for all cotton stakeholders worldwide. Currently, 43 weeds species are resistant to glyphosate and the number is increasing at an alarming rate. Soil residual/pre-emergence (PRE) herbicides like Pendimethalin and S-metolachlor can be effectively used for the control of GR weeds; however, their use is very limited at farmer’s side due to the adoption of herbicide-tolerant technology with complete reliance on glyphosate. The present study was conducted to evaluate the performance of PRE and post-emergence (POST) herbicides in glyphosate-tolerant (GT) cotton. The herbicide treatments were pendimethalin and S-metolachlor as PRE-residual, and glyphosate was applied as POST at 20 days after sowing (DAS) either alone or in combination with other herbicides like S-metolachlor, pendimethalin, and haloxyfop. A second application of glyphosate was made at 35 DAS. Results revealed that pendimethalin and S-metolachlor treatments gave 100% suppression of all dominant weeds and increased lint yield by 310–350% as compared to weedy control. In contrast, glyphosate applied once and twice, gave weed biomass reduction of only 10–86%, and increased lint yield by 136–185% over weedy control. This research established that PRE application of pendimethalin and S-metolachlor can be included in the weed management program of GT cotton.