Many Italian ryegrass populations in Oregon are resistant to more than one herbicide; therefore, the resistance patterns of these populations must be determined to identify alternative herbicides for management. Two suspected resistant Italian ryegrass populations (R2 and R4) survived flufenacet plus metribuzin applications under typical winter wheat production conditions. Populations R2 and R4 were resistant to clethodim, pinoxaden, quizalofop, mesosulfuron-methyl, flufenacet, but not to acetochlor, dimethenamid-p, metolachlor, pyroxasulfone, imazapyr, sulfometuron, or glyphosate. R4 was resistant to diuron, but R2 was not. The estimated flufenacet doses required for 50% growth reduction (GR50) were 438 g ai ha−1 (R2) and 308 g ai ha−1 (R4). Both populations were controlled by pyroxasulfone at rates greater than 15 g ai ha−1. An Asp-2078-Gly substitution in the ACCase gene was found in both populations, while an Ile-2041-Asn was found only in the R4 population. A Ser-264-Gly substitution in psbA gene was found in the R4 population. These mutations previously have been reported to provide resistance to ACCase and photosynthetic inhibitors, respectively. No resistance mutations were identified in the acetolactate synthase (ALS) gene of either population. The addition of the P450 inhibitor, chlorpyrifos, increased the injury resulting from mesosulfuron-methyl on both resistant populations providing indirect evidence that the ALS resistance may be metabolic. Multiple herbicide-resistant Italian ryegrass populations were identified in this study with both target site and nontarget site based mechanisms likely involved. However, several herbicides were identified including pyroxasulfone, a herbicide in the same group as flufenacet, which could be used to control these two populations.