Climate change poses a serious threat to biodiversity and unprecedented challenges to the preservation and protection of natural landscapes. We evaluated how climate change might affect vegetation in 22 of the largest and most iconic protected area (PA) complexes across North America. We use a climate analog model to estimate how dominant vegetation types might shift under mid- (2041-2070) and late-century (2071-2100) climate according to the RCP 8.5 scenario. Maps depicting vegetation for each PA and time period are provided. Our analysis suggests that half (11 of 22) of the PAs may have substantially different vegetation by late-21st century compared with reference period conditions. The overall trend is toward vegetation associated with warmer or drier climates (or both), with near complete losses of alpine communities at the highest elevations and high latitudes. At low elevation and latitudes, vegetation communities associated with novel climate conditions may assemble in PAs. These potential shifts, contractions, and expansions in vegetation portray the possible trends across landscapes that are of great concern for conservation, as such changes imply cascading ecological responses for associated flora and fauna. Overall, our findings highlight the challenges managers may face to maintain and preserve biodiversity in key PAs across North America.