Downy brome has converted millions of hectares of Great Basin rangelands from shrubland to annual grass-dominated systems. Methods for removing downy brome from sites that already have perennial grasses established are especially needed because of the difficulty in re-establishing perennial species. In this study, early spring applications of glyphosate alone and glyphosate plus imazapic were monitored for 2 yr. Cover of downy brome was reduced from 45 to 10% by spring application of glyphosate alone and to approximately 1% with the addition of imazapic. Perennial grass cover was not affected by the spring application of glyphosate. The addition of imazapic reduced perennial grass cover in the first year; however, it recovered by the second year. The selective response to glyphosate may be due to differences in growth stage or dormancy characteristics between annual and perennial species. Our findings suggest spring application of glyphosate may provide an alternative approach for managing annual grasses on Great Basin rangelands.