Field experiments were conducted to determine weed control and radish (Raphanus sativus) response to S-metolachlor on organic soil in the Everglades Agricultural Area (EAA) using a dose–response bioassay. S-metolachlor was applied preemergence at 0.35, 0.7, 1.4, 2.8, 5.6, and 11.2 kg·ha−1. The rate of S-metolachlor required to provide 90% weed control (ED90) and result in 5% and 10% radish injury were determined by fitting a three-parameter log-logistic model. The ED90 values for common lambsquarters, spiny amaranth, and fall panicum control were 2.7, 1.6, and 1.2 kg·ha−1 of S-metolachlor, respectively, at 14 days after treatment (DAT). At 28 DAT, the ED90 values were 3.8, 1.9, and 1.5 kg·ha−1 of S-metolachlor, respectively. Injury on radish increased as S-metolachlor rates increased with maximum injury of 24% and 19% at 14 and 28 DAT, respectively. S-metolachlor at 2.1 and 3.1 kg·ha−1 at 14 DAT and 2.6 and 3.7 kg·ha−1 at 28 DAT would result in 5% and 10% radish injury, respectively. Radish yield decreased with increasing rates of S-metolachlor. At the proposed S-metolachlor use rate of 1.4 kg·ha−1 for root crops, radish yield was 80% of the weed-free yield probably resulting from competition from common lambsquarters, which was controlled 74%. These results show that preemergence S-metolachlor would provide effective control of spiny amaranth and fall panicum in radish on organic soils of the EAA at the proposed use rate for root crops while about three times the proposed use rate would be required to provide effective common lambsquarters control. This implies that infestation of common lambsquarters on radish fields on organic soils will not be effectively controlled by S-metolachlor at the proposed use rate resulting in yield reduction.