Disturbances such as wildfire create time-sensitive windows of opportunity for invasive plant treatment, and the timing of herbicide application relative to the time course of plant community development following fire can strongly influence herbicide effectiveness. We evaluated the effect of herbicide (imazapic) applied in the first winter or second fall after the 113,000 ha Soda wildfire on the target exotic annual grasses and also key non-target components of the plant community. We measured responses of exotic and native species cover, species diversity, and occurrence frequency of shrubs and forbs seeded before (1 to 2 or 9 to 10 mo) herbicide application. Additionally, we asked whether landscape factors, including topography, species richness, and/or soil characteristics, influenced the effectiveness of imazapic. Cover of exotic annual grass cover, but not of deep-rooted perennial bunchgrass, was less where imazapic had been applied, whereas more variability was evident in the response of Sandberg bluegrass (Poa secunda J. Presl) and seeded shrubs and forbs. Regression-tree analysis of the subset of plots measured both before and after the second fall application revealed greater reductions of exotic annual grass cover in places where their cover was <42% before spraying. Otherwise, imazapic effects did not vary with the landscape factors we analyzed.