Short-lived nonnative species that become invasive are major agents of change in the American West, and they may interact with fire to have compounding negative effects on ecosystem function. As public lands come under increasing stress from invader–fire interactions, managers need tools that deplete nonnative propagules at meaningful temporal and spatial scales. The pre-emergent herbicide indaziflam, which has been approved for use in natural areas, achieves multi-year control of Bromus tectorum (cheatgrass) and other short-lived nonnative species, while leaving co-occurring, established perennials largely intact. Here we explore how pre-fire management with indaziflam shapes plant community assembly post-fire. We ask whether indaziflam (1) maintains good efficacy against the target species Bromus tectorum, Bromus japonicus, and Alyssum simplex in the first growing season post-wildfire, as well as short-lived introduced species more generally; (2) exhibits nontarget effects on short-lived native species; and (3) supports recovery of long-lived native species. Indaziflam was highly effective in controlling all three target species in both burned and unburned areas, revealing its potential to break the invader–fire cycle. However, short-lived native species were also suppressed, either in burned areas only (richness), or in burned and unburned areas (percent cover). As found in other systems, indaziflam had no negative effects on long-lived native species. These findings highlight potential trade-offs in adopting indaziflam as a tool, with its use likely to be extremely effective in highly invaded systems already depauperate of native propagules, but requiring more caution and, if resources allow, attendant restoration plans (e.g., reseeding with desirable natives) in more intact natural areas.