Buffelgrass (Pennisetum ciliare) is a fire-prone, African bunchgrass spreading rapidly across the southern Arizona desert. This article introduces a model that simulates buffelgrass spread over a gridded landscape over time to evaluate strategies to control this invasive species. Weed-carrying capacity, treatment costs, and damages vary across grid cells. Damage from buffelgrass depends on its density and proximity to valued resources. Damages include negative effects on native species (through spatial competition) and increased fire risk to land and buildings. We evaluate recommended “rule of thumb” control strategies in terms of their ability to prevent weed establishment in newly infested areas and to reduce damage indices over time. Two such strategies—potential damage weighting and consecutive year treatment—used in combination, provided significant improvements in long-term control over no control and over a strategy of minimizing current damages in each year. Results suggest specific recommendations for deploying rapid-response teams to prevent establishment in new areas. The long-run population size and spatial distribution of buffelgrass is sensitive to the priority given to protecting different resources. Land managers with different priorities may pursue quite different control strategies, posing a challenge for coordinating control across jurisdictions.