Southwest Wyoming's wildlife and habitat resources are increasingly affected by energy and urban/exurban development, climate change, and other key drivers of ecosystem change. To ensure that southwest Wyoming's wildlife populations and habitats persist in the face of development and other changes, a consortium of public resource-management agencies proposed the Wyoming Landscape Conservation Initiative (WLCI), the overall goal of which is to implement conservation actions. As the principal agency charged with conducting WLCI science, the U.S. Geological Survey (USGS) has developed a Science Strategy for the WLCI. Workshops were held for all interested parties to identify and refine the most pressing management needs for achieving WLCI goals. Research approaches for addressing those needs include developing conceptual models for understanding ecosystem function, identifying key drivers of change affecting WLCI ecosystems, and conducting scientific monitoring and experimental studies to better understand ecosystems processes, cumulative effects of change, and effectiveness of habitat treatments. The management needs drive an iterative, three-phase framework developed for structuring and growing WLCI science efforts: Phase I entails synthesizing existing information to assess current conditions, determining what is already known about WLCI ecosystems, and providing a foundation for future work; Phase II entails conducting targeted research and monitoring to address gaps in data and knowledge during Phase I; and Phase III entails integrating new knowledge into WLCI activities and coordinating WLCI partners and collaborators. Throughout all three phases, information is managed and made accessible to interested parties and used to guide and improve management and conservation actions, future habitat treatments, best management practices, and other conservation activities.