Reserve design is a process that can address ecological, social, and political factors to identify parcels of land needed to sustain wildlife populations and other natural resources. Acquisition of parcels for a large terrestrial reserve is difficult because it typically occurs over a long timeframe and thus invokes consideration of future conditions such as climate and urbanization changes. In central Florida, a new protected area, the Everglades Headwaters National Wildlife Refuge, has been authorized by the United States Government. The new refuge will host important threatened and endangered species and habitats, as well as be located to allow for species adaptation from climate change impacts. For this study we combined habitat objectives defined by the U.S. Fish and Wildlife Service and projections from two urbanization models to provide guidance for Everglades Headwaters National Wildlife Refuge design. We used Marxan with Zones to find near-optimal solutions for protecting explicit amounts of five target habitats. We identified parcels for inclusion into the reserve design that the model allocated among two zones representing different methods of protection: fee-simple purchase (up to 20,234 hectares authorized by the United States government), and conservation easement agreements (up to 40,469 hectares authorized). As expected, for all scenarios we found an increase in costs as the proportion of fee-simple purchases was increased, reflecting the lesser cost of easements, but the number of parcels required for protection differed little among scenarios. The two urbanization models showed considerable agreement over which habitat patches were not forecast to be developed, and showed some agreement over which parcels might be developed. The U.S. Fish and Wildlife Service may benefit from focusing on parcels that are selected frequently by our analyses under both urban scenarios because these parcels are more likely to be in areas where urbanization threats and demand for land is reduced. The reserve designs we generated met U.S. Fish and Wildlife Service habitat goals within fee and easement zone restrictions, and we found reserve configurations that fell well below the mandated size limit.