Quinclorac controls crabgrass (Digitaria spp.) post-emergence in cool- and warm-season turfgrass. A rate response study revealed that two Mississippi smooth crabgrass (Digitaria ischaemum) species (MSU1 and MSU2) are resistant to quinclorac. Following that, field experiments were carried out to evaluate programmatic approaches to control one of these populations. Despite prior study on quinclorac-resistant weeds, to date, quinclorac-resistant smooth crabgrass and its mechanism of resistance have only been reported once in California. The mechanism of resistance of MSU1 and MSU2 relative to susceptible (SMT) was then investigated. The SMT biotype accumulated three times more cyanide than the resistant populations. Glutathione-S-transferase (GST) activity was evaluated as a possible contributor to non-target site resistance. The GST activity was elevated in the MSU1 and MSU2 populations. These findings suggest a non-target site–based mechanism of resistance involving the accumulation of cyanide. Further research is needed to investigate potential target-site mechanisms of resistance.