Pacific Lamprey (Entosphenus tridentatus) are a native anadromous species that, like salmon, historically returned to spawn in large numbers in watersheds along the west coast of the United States (U.S.). Lamprey play a vital role in river ecosystems and are one of the oldest vertebrates that have persisted over time likely influencing the evolution of many aquatic species. Pacific Lamprey have declined in abundance and are restricted in distribution throughout Washington, Oregon, Idaho and California. A key uncertainty influencing Pacific Lamprey status is the impact of climate change. We modified the NatureServe Climate Change Vulnerability Index (CCVI) to accommodate climate predictions from the International Panel on Climate Change. Using downscaled information, we characterized changes in 15 rivers occupied by Pacific Lamprey in the western U.S. We evaluated this risk under Representative Concentration Pathways (RCP) 4.5 and 8.5 for two time periods (mid-century 2040–2069 and end-century 2070–2099). The CCVI scores generally increased when going from RCP 4.5 to RCP 8.5 in three Global Climate Models for both mid-century and end-century, which our analyses forecasts degraded stream temperature and hydrologic conditions under increasing greenhouse gas emissions. The geographically assessed results suggest that climate change impacts to Pacific Lamprey vulnerability are magnified in highly altered rivers. If we continue to observe greenhouse gas emission levels associated with the RCP 8.5, Pacific Lamprey will be at greater risk to climate change impacts. In order to mitigate the risk from climate change toward the end of the century, additional actions will need to be prioritized to rapidly reduce the impact of these threats such as increasing flow, creating backwater habitat, restoring riparian vegetation and reducing stream disturbances. The findings revealed the patterns of vulnerability for Pacific Lamprey across their U.S. range are informative for prioritizing river restoration actions when paired with regional implementation plans.