Decision-makers in Afghanistan, China, India, and Pakistan must reconcile a host of overlapping socioeconomic, ecological, and policy pressures to ensure their countries’ future water needs. Growing populations and expanding economies are driving rising water demands, even as environmental degradation and unsustainable consumption practices increasingly stretch the shared resources of the Indus River. Climate change will compound the challenges confronting water managers. None of the riparian states can successfully surmount these tests on its own. Greater dialogue and coordination among the basin’s diverse communities offers considerable scope for mitigating mutual threats and generating collective benefits. Collaborative approaches promoting data exchange, capacity building, and knowledge generation can help policymakers and the broader public better apprehend and assess the basin’s complex climate and water challenges. Common frameworks for identifying and adopting policy lessons can enlarge the range of policy choices, scale up best practices, and chart cooperative pathways forward.