Medusahead is an aggressive, nonnative, winter annual grass that infests rangelands in the western United States. Its ability to rapidly spread, outcompete native vegetation, and destroy forage potential is a primary concern for landowners and land managers exposed to this weed. Prescribed burns were conducted at a low- and high-litter site in northern Utah prior to conducting experiments to evaluate the effects of fall and spring applications of sulfometuron at 39 or 79 g ai/ha and imazapic at 70 or 140 g ai/ha on medusahead and associated perennial grasses, annual and perennial forbs, and bare ground cover. Large differences in pretreatment medusahead litter between the sites resulted in less surface area burning at the low-litter site (∼10%) compared to the high-litter site (∼80%). Higher herbicide rates significantly increased medusahead control and bare ground cover; however, this rate affect largely depended on site, season, and herbicide. The low- and high-litter sites did not differ significantly in perennial grass cover 2 yr after burning. Annual forb cover was greater, but perennial forb cover was lower at the low-litter site compared to the high-litter site. Several treatment combinations were identified as having the potential to maintain greater than 50% medusahead control in the second year after herbicide applications. These results collectively demonstrate that potential exists to successfully control medusahead and produce a window of opportunity to reintroduce a greater abundance of perennial species back into the plant community via seeding.