Herbicide resistance to several of the most common weed species in US rice production, such as barnyardgrass and red rice, has made weed control extremely difficult with available herbicide options. No very-long-chain fatty acid–inhibiting herbicides are labeled for use in US rice; however, pethoxamid is one such herbicide under development for soil-applied use to control grasses and small-seeded broadleaves in rice and various row crops. Field trials were conducted in 2015 and 2016 near Stuttgart, AR, for rice tolerance and in 2016 near Colt, AR, and Lonoke, AR, for weed control with the use of pethoxamid-containing rice herbicide programs. Pethoxamid was applied alone and in a program at 420 and 560 g ai ha–1 with other herbicides labeled in rice including clomazone, quinclorac, propanil, imazethapyr, and carfentrazone POST. Injury less than 10% was seen for all treatments 2 wk after application in 2015 and 2016, except for pethoxamid at 420 g ha–1 to clomazone to one-leaf rice. Rice injury dissipated to less than 5% following all treatments by 4 wk after flood establishment. Barnyardgrass was controlled 95% or more near Colt and 93% or more near Lonoke for herbicide programs including clomazone PRE followed by pethoxamid plus quinclorac or imazethapyr at three- to four-leaf stage rice. Considering the minimal injury and high levels of barnyardgrass control associated with pethoxamid-containing weed control programs, pethoxamid provides a unique and effective site of action for use in US rice production.