Abstract Effective weed control is critical to growth and development of flue‐cured tobacco; however, current herbicide options are limited in commercial production. Field experiments were conducted from 2017 to 2018 to evaluate S ‐metolachlor for use in flue‐cured tobacco weed management programs. Treatments included 10 herbicide programs: pretransplanted incorporated (PTI) applications of S ‐metolachlor (1.07 kg a.i. ha –1 ) alone or in various combinations with sulfentrazone (0.18 kg a.i. ha –1 ), clomazone (0.84 kg a.i. ha –1 ), and pendimethalin (0.79 kg a.i. ha –1 ). S ‐metolachlor and pendimethalin were also applied posttransplanting directed to row middles (POST‐DIR) following PTI applications of sulfentrazone + clomazone. A single posttransplanting over‐the‐top (POST‐OT) application of S ‐metolachlor and a non‐treated control were included for comparison. The inclusion of S ‐metolachlor in PTI herbicide programs did not improve weed control beyond the combination of sulfentrazone + clomazone. However, weed control after final harvest was improved by 8%, when S ‐metolachlor was applied POST‐DIR. S ‐metolachlor applied POST‐OT caused injury to tobacco plants (12%), although symptoms were transient with less than 2% visual injury 6 wk after transplanting. Due to increased weed control through harvest and the low injury potential, our results suggest that POST‐DIR applications of S ‐metolachlor are the best fit for flue‐cured tobacco production when used in conjunction with recommended PTI herbicide programs.