Climate change poses an urgent threat to biodiversity that demands societal responses. The magnitude of this challenge is reflected in recent international commitments to protect 30% of the planet by 2030 while adapting to climate change. However, because climate change is global, interventions must transcend political boundaries. Here, using the California Bight as a case study, we provide 21 biophysical guidelines for designing climate-smart transboundary marine protected area (MPA) networks and conduct analyses to inform their application. We found that future climates and marine heatwaves could decrease ecological connectivity by 50% and hinder the recovery of vulnerable species in MPAs. To buffer the impacts of climate change, MPA coverage should be expanded, focusing on protecting critical nodes for the network and climate refugia, where impacts might be less severe. For shared ecoregions, these actions require international coordination. Our work provides the first comprehensive framework for integrating climate resilience for MPAs in transboundary ecoregions, which will support other nations’ aspirations.