Acetochlor, a chloroacetamide herbicide, is now registered for preplant (PPI), preemergence (PRE), and postemergence (POST) application in peanut. Field research was conducted during 2011 and 2012 in Georgia and North Carolina to determine peanut response and weed control by acetochlor compared with S-metolachlor alone and in programs with other herbicides. In weedfree experiments, peanut tolerance to acetochlor (1.26 and 2.52 kg ai/ha) and S-metolachlor (1.42 kg ai/ha) were evaluated when applied PPI, PRE, early postemergence (EPOST), or POST. Peanut tolerance to acetochlor was similar to S-metolachlor with no negative impact of either herbicide on peanut yield compared with non-treated peanut in absence of weed interference. When applied PRE, acetochlor controlled Palmer amaranth, pitted morningglory, sicklepod, and Texas millet similarly to S-metolachlor while control of broadleaf signalgrass was greater with S-metolachlor. Weed control programs containing EPOST and/or POST applications of herbicides following PRE herbicides provided the best overall weed control but did not affect yellow nutsedge control regardless of whether acetochlor or S-metolachlor were applied. Herbicide programs including PRE, EPOST, and POST herbicides most often resulted in the greatest yields. There was no difference in peanut yield regardless of the presence of acetochlor or S-metolachlor in a comprehensive herbicide program.