Field surveys were conducted across the Blacklands region of Texas during 2016 and 2017 to document the distribution of herbicide-resistant Lolium spp. infesting winter wheat production fields in the region. A total of 68 populations (64 Italian ryegrass, four perennial ryegrass) were evaluated in a greenhouse for sensitivity to herbicides of three different modes of action: an acetolactate synthase (ALS) inhibitor (mesosulfuron-methyl), two acetyl-coenzyme-A carboxylase (ACCase) inhibitors (diclofop-methyl and pinoxaden), and a 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibitor (glyphosate). Herbicides were applied at twice the label-recommended rates for mesosulfuron-methyl (29 g ai ha−1), diclofop-methyl (750 g ai ha−1), and pinoxaden (118 g ai ha−1); and at the recommended rate for glyphosate (868 g ae ha−1). The herbicide screenings were followed by dose-response assays of the most-resistant ryegrass population for each herbicide at eight rates (0.5, 1, 2, 4, 8, 16, 32, and 64×), compared with a susceptible population at six rates (0.0625, 0.125, 0.25, 0.5, 1, and 2×). The initial screening and dose-response experiments were conducted in a completely randomized design with three replications and two experimental runs. Survivors (<80% injury) were characterized as highly resistant (0% to 20% injury) or moderately resistant (21% to 79%). Results showed that 97%, 92%, 39%, and 3% of the Italian ryegrass populations had survivors to diclofop-methyl, mesosulfuron-methyl, pinoxaden, and glyphosate treatments, respectively. Of the four perennial ryegrass populations, three were resistant to diclofop-methyl and mesosulfuron-methyl, and one was resistant to pinoxaden as well. Perennial ryegrass populations did not exhibit any resistance to glyphosate. Dose-response assays revealed 37-, 196-, and 23-fold resistance in Italian ryegrass to mesosulfuron-methyl, diclofop-methyl, and pinoxaden, respectively, compared with a susceptible standard. One Italian ryegrass population exhibited three-way multiple resistance to ACCase-, ALS-, and EPSPS-inhibitors. The proliferation of multiple herbicide–resistant ryegrass is a challenge to sustainable wheat production in Texas Blacklands and warrants diversified management strategies.