Across the Great Barrier Reef (GBR), outbreaks of Crown of Thorns starfish (COTS) are responsible for significant losses of coral cover. Currently, culling by divers on control vessels is the most effective management technique for suppressing outbreaks. However, given the size of the GBR and the substantial effort required to reduce COTS densities below specific ecological thresholds, culling across the entire GBR is implausible. As such, selection of which reefs to cull to have the greatest benefit in terms of coral cover saved and number of COTS culled is challenging. Using an ecosystem model of the GBR which includes both coral and COTS population dynamics, we simulated a range of control scenarios which represent realistic strategies that reef managers might adopt. These scenarios evaluated the benefit of allocating vessels to: 1) specific regions; 2) the initiation box(es) in the Swains and/or north of Cairns; and 3) reefs that are substantial sources/sinks of COTS with high coral cover. We compared the effectiveness of these scenarios in the context of different climate change projections. We then give recommendations for which strategies to consider to improve the effectiveness of the COTS control program on the GBR.