Phalaris brachystachys (short-spiked canary grass) is considered to be among the most troublesome cereal weeds in Mediterranean areas. A bioeconomic model, based on population dynamics, competition and economic sub-models, was developed to simulate the long-term economic consequence of using herbicide-based strategies: no herbicide application, full herbicide dose (standard rate) and two reduced dose rates (75 and 50% of the standard rate) to control P. brachystachys in a biennial wheat–sunflower rotation. Simulation results indicated that only herbicide application at a full dose (90% control) and 3/4 dose (80% control) produced positive economic results, with the full dose being the best strategy (EUR 98.65 ha−1 year−1). A sensitivity analysis showed that the economic outcome, in terms of annualized net return, was strongly influenced by changes in yield, price, and fixed costs. In addition, the annualized net return was more sensitive to parameter changes at reduced herbicide doses than at full rate. In the wheat–sunflower rotation system, the application of the full dose of herbicide was the most economical and stable strategy in the long-term. Reduced doses are not a recommended option from an economic point of view. Bioeconomic models provide practical insight into different management approaches for effective weed control.