With the introduction of tetflupyrolimet as the first herbicide with a novel site of action in the last three decades, screening for herbicide resistance before commercialization has become integral to ensure successful applications. In the mid-southern United States, tetflupyrolimet is anticipated to be used as a preemergence (PRE) herbicide for barnyardgrass control but does exhibit postemergence (POST) herbicidal activity. In 2020, 45 Echinochloa crus-galli (barnyardgrass) accessions were collected from rice-producing areas in Arkansas and were screened in the greenhouse to tetflupyrolimet at 134 g ai ha-1 PRE and POST at the 2- to 3-leaf growth stage on a silt loam soil. A field experiment was conducted where tetflupyrolimet was applied alone at 134 g ai ha-1 or with clomazone at 336 g ai ha-1, to a susceptible barnyardgrass standard and four other accessions with confirmed resistance to florpyrauxifen-benzyl, imazethapyr, propanil, and quinclorac at the spiking, 1-, 2-, 3-, and 4-leaf stages. For the PRE screening, the percent visible control ranged from 88% to 99%, with some accessions differing in sensitivity to tetflupyrolimet. Percent mortality ranged from 47% to 90% at the PRE timing. Visible control and mortality ranged from 63% to 88% and 7% to 65%, respectively, from a POST application, suggesting there is differential sensitivity and that foliar applications may not be as effective as soil applications. In the field experiment, barnyardgrass accession did not influence POST biomass production and was impacted more by the growth stage at application, although the difference was frequently numerical. In general, applying tetflupyrolimet alone or with clomazone to ≥3 leaf grass compromised performance. Tetflupyrolimet will be better optimized as a soil-applied herbicide in mid-southern U.S. rice culture.