Climate change uncertainty poses serious challenges to conservation efforts. One emerging conservation strategy is to identify and conserve climate change refugia: areas relatively buffered from contemporary climate change that enable persistence of valued resources. This management paradigm may be pursued at broad scales by leveraging existing resources and placing them into a tangible framework to stimulate further collaboration that fosters management decision-making. Here, we describe a framework for moving toward operationalizing climate change refugia conservation at an ecoregion scale with an analysis for the Sierra Nevada ecoregion (CA, USA). Structured within the Climate Change Refugia Conservation Cycle, we identify a preliminary suite of conservation priorities for the ecoregion, and demonstrate how existing mapping, data, and applications could be used for identifying, prioritizing, managing, and monitoring refugia. We focus on six stakeholder-identified conservation priorities, including two process-based refugial priorities (snow and fire), and four ecosystem-based refugial priorities (meadows, giant sequoia, old growth forests, and alpine communities). This pilot overview of concepts and resources provides a foundation for both near-term implementation and further discussion in moving from science to conservation practice. Such an approach may provide new practical insights for ecosystem management at ecoregion scales in the face of climate change.