Wetlands are more threatened than any other ecosystem type, with losses exceeding 50% of their original extent worldwide. Despite the small portion of the Earth's surface that they comprise, wetlands contribute significantly to global ecosystem services. In this study, we tested the hypothesis that the location and rate of change in wetland amount in the Tempisque Basin of northwest Costa Rica is predictable from landscape setting. Our results demonstrate that a strong potential exists for developing predictive models of wetland conversion based on an understanding of wetland location and surrounding trends of land use. We found that topography was the single most important predictor of wetland conversion in this area, entraining other conversion processes, and that spatial patterns of wetland loss could consistently be predicted from landscape-level variables. Areas with highest probabilities of conversion were found in the most accessible, non-protected regions of the landscape. While Palo Verde National Park made a substantial contribution to wetland conservation, our results highlight the dependence of lower-lying protected areas on upland processes, adding a little-addressed dimension of complexity to the dialogue about protected area management. Conservation strategies aimed at reducing wetland loss in tropical habitats will benefit from careful analysis of the dominant land use system(s) at a relatively broad scale, and the subsequent development of management and policy responses that take into account dynamic opportunities and constraints in the landscape.