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Currently, there are seven herbicides labeled for U.S. tobacco production; however, additional modes of action are greatly needed in order to reduce the risk of herbicide resistance. Field experiments were conducted at five locations during the 2017 and 2018 growing seasons to evaluate flue-cured tobacco tolerance to S-metolachlor applied pretransplanting incorporated (PTI) and pretransplanting (PRETR) at 1.07 (1×) and 2.14 (2×) kg ai ha−1. Severe injury was observed 6 wk after transplanting at the Whiteville environment in 2017 when S-metolachlor was applied PTI. End-of-season plant heights from PTI treatments at Whiteville were likewise reduced by 9% to 29% compared with nontreated controls, although cured leaf yield and value were reduced only when S-metolachlor was applied PTI at the 2× rate. Severe growth reduction was also observed at the Kinston location in 2018 where S-metolachlor was applied at the 2× rate. End-of-season plant heights were reduced 11% (PTI, 2×) and 20% (PRETR, 2×) compared with nontreated control plants. Cured leaf yield was reduced in Kinston when S-metolachlor was applied PRETR at the 2× rate; however, treatments did not impact cured leaf quality or value. Visual injury and reductions in stalk height, yield, quality, and value were not observed at the other three locations. Ultimately, it appears that injury potential from S-metolachlor is promoted by coarse soil texture and high early-season precipitation close to transplanting, both of which were documented at the Whiteville and Kinston locations. To reduce plant injury and the negative impacts to leaf yield and value, application rates lower than 1.07 kg ha−1 may be required in these scenarios.