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Excessive phosphorus (P) export to aquatic ecosystems can lead to impaired water quality. There is a growing interest among watershed managers in using restored wetlands to retain P from agricultural landscapes and improve water quality. We develop a novel framework for prioritizing wetland restoration at a regional scale. The framework uses an ecosystem service model and an optimization algorithm that maximizes P reduction for given levels of restoration cost. Applying our framework in the Lake Champlain Basin, we find that wetland restoration can reduce P export by 2.6% for a budget of $50 M and 5.1% for a budget of $200 M. Sensitivity analysis shows that using finer spatial resolution data for P sources results in twice the P reduction benefits at a similar cost by capturing hot-spots on the landscape. We identify 890 wetlands that occur in more than 75% of all optimal scenarios and represent priorities for restoration. Most of these wetlands are smaller than 7 ha with contributing area less than 100 ha and are located within 200 m of streams. Our approach provides a simple yet robust tool for targeting restoration efforts at regional scales and is readily adaptable to other restoration strategies.