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Background: Wild oat (Avena fatua L.) is a self-pollinating, allohexaploid species in the family Gramineae (grasses), which is a malignant weed that mainly harms crops such as wheat. In recent years, a decline in the control efficiency of flucarbazone-sodium against wild oat has occurred in some regions of China. Results: We identified an ALS-resistant A. fatua population (R population). Whole-plant response assays revealed that the R population exhibited a moderate level of resistance (5.9-fold) to flucarbazone-sodium. Pre-treatment with malathion significantly reduced flucarbazone-sodium resistance in the R population. The known mutation sites and ALS gene relative expression that confer resistance to ALS inhibitor herbicides were not found in R population. Following flucarbazone-sodium treatment, the expression of eight genes related to metabolic enzymes was investigated using quantitative real-time PCR (qRT-PCR). CYP92A6 and the Aldo/keto reductase family were highly expressed in the R population after the application of flucarbazone-sodium. Conclusions: The mechanism of flucarbazone-sodium resistance in A. fatua is mediated by NTSR, nor TSR. Two genes, CYP92A6 and the Aldo/keto reductase family, were discovered to be possibly related in the metabolism of NTSR in the A. fatua population, justifying more functional studies. The results will serve as a data resource for further studies on the molecular mechanisms of A. fatua to flucarbazone-sodium. [ABSTRACT FROM AUTHOR]