The invasive annual grass downy brome (Bromus tectorum L.) is a critical threat to the semiarid shrublands that characterize western North America. More abundant fine fuel after invasion typically increases fire frequency in plant communities adapted to relatively infrequent burning, reducing the likelihood of native plant persistence. Currently, imazapic is most often used to manage B. tectorum, but reinvasion from the seedbank after treatment is common. Indaziflam is a newer herbicide recently labeled for use in rangelands grazed by livestock, and many research trials have demonstrated its ability to deplete invasive annual grass seedbanks. We evaluated the effectiveness of indaziflam and imazapic for reducing B. tectorum density and cover over a period of approximately 5 yr (57 mo after treatment [MAT]) at two invaded sagebrush-grassland sites near Pinedale, WY. Treatments included three different indaziflam rates (51, 73, and 102 g ai ha−1) and one imazapic rate (123 g ai ha−1), and these treatments were reapplied to half of each plot at 45 MAT to evaluate the effects of two sequential applications. We also measured perennial grass cover, because positive perennial grass responses were observed after release from B. tectorum competition in other studies, and perennial grasses may provide resistance to B. tectorum reinvasion. Intermediate and high indaziflam rates (73 and 102 g ha−1, respectively) reduced B. tectorum cover and density at 45 MAT, and perennial grass cover responded positively to some treatments, mostly early in the study (≤33 MAT). Imazapic reduced B. tectorum initially, but did not affect density or cover at either site beyond 21 MAT. Reapplication did not substantially improve B. tectorum control at 57 MAT in plots treated with intermediate and high indaziflam rates, suggesting that long-term control with a single indaziflam treatment may be possible in some cases.