The Philadelphia philanthropy termed the initiative an "unprecedented collaboration" bringing together 40-plus regional and national groups.
"This is one of the largest philanthropic investments in watersheds ever," said Peter Howell, executive vice president of the Open Space Institute, based in New York, which is managing the largest grant, $10.2 million.
Much of it will be used for land conservation, and the institute is targeting projects where the funds can be matched 3-1, for an additional $27 million worth of projects.
For the foundation, "it is among the largest if not the largest dedication of grants to one specific strategy," said its senior program officer for watershed protection, Andrew Johnson.
More important, he said, the grants are deliberately connected to one another. "We're lining them up so they have collective impact," he said. "We've created a framework that other funders will find useful to inform their own grant-making.
"We're trying to make opportunity happen."
The National Fish and Wildlife Foundation will get $7 million to "regrant" to groups that will plant trees, restore stream banks, help farmers incorporate better methods to reduce water pollution, and teach communities how to lessen or better manage storm water.
Amanda Bassow, director of the group's eastern partnership office, said she would be looking for matching grants from federal and other private sources to triple the pool of project money.
The Academy of Natural Sciences of Drexel University will get $3.2 million to gather data on projects and their effects.
A large cadre of scientists will be pulling on hip boots and wading into streams to collect the baseline data that's often overlooked, and build from there. They'll be live-tweeting from the field and publishing in peer-reviewed scientific journals.
"It's really about telling the full story of what's happening in the basin and how the water quality is being affected by the work that's being done," said Roland Wall, the academy's senior director for environmental initiatives.
The initiative does not directly address one of the most contentious and potentially most transformative issues in the basin - natural gas development.
But the issue hovers at the edges. Some projects involve related matters, such as evaluating the importance of forested headwaters that could be fragmented by drilling pads and access roads.
The Delaware, fed by 216 tributaries, is the longest undammed river in the East and has been called one of the hardest-working, most productive basins in the country. It provides drinking water for 15 million people - 5 percent of the U.S. population.
By many measures, its water quality has improved greatly in recent decades. But development has burgeoned, increasing pavement and other impervious surfaces. Agriculture and storm-water runoff pollute streams. Deforestation continues.
The core idea of the William Penn initiative, years in the planning, is to build on the successes and deal with the new stresses.
Rather than focusing on the whole basin, which spans more than 13,500 square miles and stretches from New York to the mouth of the Delaware Bay, the foundation selected eight sub-watersheds or watershed "clusters."
In places with good water quality - such as in the Upper Lehigh, where only 2 percent of stream miles are considered impaired - the idea is to figure out how to preserve it.
In areas with challenges - notably, the Wissahickon and other urban watersheds in the Philadelphia suburbs, where 94 percent of stream miles are impaired - the goal is to figure out how to restore the water quality.
"Being an urban area, a lot of people don't even know there's a creek down there. They don't have a clue where it comes from or what purpose it serves. They don't know if there are fish in it," said Patrick Starr, an executive vice president with the Pennsylvania Environmental Council, which is the lead agency in that region.
"What's important is that we're going to be doing actual restoration projects in these communities, and tying that back to community education and awareness," he said.
"I'm always talking about death by a thousand cuts. This is more like restoration and life by a thousand sutures or stitches," he added. "We have to put it back together."
The Brandywine and Christina watershed, with its headwaters in northern Chester County, faces degradation from agricultural practices, such as letting cows wade in streams.
About 500,000 people rely on the Brandywine for drinking water, and Wilmington water officials have already determined it makes financial sense to put funds into upstream improvements instead of water plant treatments, said Sherri L. Evans-Stanton, director of the Brandywine Conservancy, the lead agency.
In that cluster, the groups hope to build on current successes - planting trees, conserving land, and working with Plain Sect farmers in the headwaters area to alter their methods, she said.
The Middle Schuylkill cluster, including portions of Berks, Bucks and Montgomery Counties, faces degradation from agriculture and urbanization.
In South Jersey, the foundation decided to focus on the Kirkwood-Cohansey aquifer, which underlies the ecologically sensitive Pinelands and provides drinking water for many towns, including those on the Delaware Bay shore.
"The clean and cheap resource that we have of water in the Kirkwood-Cohansey is finite and threatened - by development, by overuse and, in certain areas, direct contamination," said Chris Jage, with the New Jersey Conservation Foundation.
The two U.S. Environmental Protection Agency regional administrators whose areas are in the basin praised the project. "EPA values collaborative initiatives like this" that leverage more resources, said Shawn M. Garvin of the Philadelphia office.