Managing invasive winter annual grasses on noncrop and rangeland remains a constant challenge throughout many regions of the United States. Currently, there are limited management options for controlling winter annual grasses that work consistently, provide multiple years of control, and do not injure desirable plant communities. Imazapic has been one of the most widely used herbicides for downy brome control on rangeland; however, control with imazapic has been inconsistent beyond the application year and perennial grass injury is not uncommon. Indaziflam, a new herbicide mode of action for rangeland weed management, has shown promise in providing long-term downy brome control. A greenhouse study was conducted to compare pre-emergence activity of imazapic and indaziflam on six invasive winter annual grasses: downy brome, cereal or feral rye, jointed goatgrass, Japanese brome, medusahead, and ventenata. For both herbicides, seven rates were used to develop dose-response curves for each species. Log-logistic regression was conducted to determine the herbicide dose required to reduce biomass by 50% (GR50 values). Indaziflam was significantly more active across all species compared to imazapic, with the exception of jointed goatgrass. Comparing all species, the GR50 values for imazapic were on average 12 times higher than indaziflam. Japanese brome was the most sensitive to both herbicides, whereas jointed goatgrass and feral rye were the most difficult winter annual grasses to control with indaziflam and imazapic, respectively. This research provides evidence of a potential new mode of action for land managers to control the major invasive winter annual grasses.