The Delaware River watershed provides drinking water to over 15 million people, critical habitat for plants and animals, including many threatened and endangered species, and recreational and economic enterprise valued at $10 billion per year in direct wages. Water quality and associated economic, environmental and social values have improved dramatically since the 1950s when the lower portion of the river was declared a dead zone during parts of the summer due to excessive inputs of domestic and industrial waste. The question today is how to ensure that progress continues in the face of persistent and growing threats to water quality. Recognizing the challenges facing the watershed, over 40 of the leading conservation groups in this 13,000 square mile region are pursuing a 10-year strategic initiative focused on water quality through the Delaware River Watershed Initiative, a conservation program advancing a combination of place-based work in watershed protection, restoration, education, collaboration and innovation through collective impact. This paper serves as an invitation for broader strategic involvement to accelerate watershed protection and restoration; it also is a springboard for stakeholders to set an agenda for ensuring that the Delaware River watershed delivers clean water for humans, plants and animals. The paper identifies eight “clusters” of sub-watersheds, constituting approximately 25 percent of the total Delaware Basin, where analysis has shown that investment in water quality could deliver significant returns. Diverse geology, land use, development patterns, population density and en-vironmental stressors are present throughout these sub-watershed clusters. Focusing conservation actions in these places contributes directly to local water quality, and by fostering experimentation and innovation, it also cultivates a wide range of effective approaches for scaling up investment across the Delaware River watershed and beyond. This paper emphasizes five strategies for investing in protection of high quality waters and restoration of impaired waters: 1. protect forested headwaters to maintain high water quality; 2. manage agricultural lands to reduce polluted runoff and increase groundwater infiltration; 3. implement best practices and new financial incentives to reduce urban stormwater pollution through natural processes; 4. increase the evidence base for watershed protection by monitoring trends in water quality and assessing project impacts; 5. improve policy and practice through applied research focused on water quality outcomes. These strategies demand place-based work, and the Delawre River Watershed Initiative will focus on advancing these efforts through the cooperation of organizations located in the eight distinct watershed clusters. Proceeding downstream from the headwaters, the eight landscapes are: Pocono Mountains and Kittatinny Ridge; New Jersey Highlands; Upper Lehigh River; Middle Schuylkill River; Schuylkill Highlands; Brandywine and Christina Rivers Upstream; Suburban Philadelphia; and Kirkwood-Cohansey Aquifer (comprising New Jersey’s Bayshore; and Pine Barrens). These clusters bring together many of the most ecologically valuable and significantly impaired areas of the watershed. They are strategically located where strong organizations and critical natural vatues provide measurable opportunities for advancing local water quality while having regional impact. The selection of areas and strategies was based on research and planning undertaken by the Open Space Institute (OSI) and the Academy of Natural Sciences of Drexel University (ANSDU} with support from the William Penn Foundation. Researchers at OSI and ANSDU were joined by the National Fish and Wildlfe Foundation (NFWF) in engaging over 40 organizations working across the eight sub-watershed clusters to develop collaborative plans for implementing and measuring local conservation strategies essential to the long-term health and vibrancy of the region. These implementation plans tackle major threats to water quality and include strategies to track progress and share lessons learned. The plans provide a framework for public agencies and philanthropic funders seeking to pursue targeted watershed protection outcomes supported by monitoring, technical assistance and ongoing communications. Organizations large and small, public and private, are invited to read this paper and consider this program as an opportunity to align investment for greater impact and help ensure a bright future for the Delaware River watershed.