Freshwater biodiversity loss is accelerating globally, but humanity can change this trajectory through actions that enable recovery. To be successful, these actions require coordination and planning at a global scale. The Emergency Recovery Plan for global freshwater biodiversity aims to reduce the risk for freshwater biodiversity loss through six priority actions: (1) accelerate implementation of environmental flows; (2) improve water quality to sustain aquatic life; (3) protect and restore critical habitats; (4) manage exploitation of freshwater species and riverine aggregates; (5) prevent and control nonnative species invasions in freshwater habitats; and (6) safeguard and restore freshwater connectivity. These actions can be implemented using future-proofing approaches that anticipate future risks (e.g., emerging pollutants, new invaders, and synergistic effects) and minimize likely stressors to make conservation of freshwater biodiversity more resilient to climate change and other global environmental challenges. While uncertainty with respect to past observations is not a new concern for freshwater biodiversity, future-proofing has the distinction of accounting for the uncertainty of future conditions that have no historical baseline. The level of uncertainty with respect to future conditions is unprecedented. Future-proofing of the Emergency Recovery Plan for freshwater biodiversity will require anticipating future changes and developing and implementing actions to address those future changes. Here, we showcase future-proofing approaches likely to be successful using local case studies and examples. Ensuring that response options within the Emergency Recovery Plan are future-proofed will provide decision makers with science-informed choices, even in the face of uncertain and potentially new future conditions. We are at an inflection point for global freshwater biodiversity loss; learning from defeats and successes can support improved actions toward a sustainable future.