The Army Corps of Engineers on Wednesday denied a permit for the proposed Pebble Mine in Alaska, likely dealing a death blow to a long-disputed project that aimed to extract one of the world’s largest deposits of copper and gold ore, but which threatened breeding grounds for salmon in the pristine Bristol Bay region.

The fight over the mine’s fate has raged for more than a decade. The plan was scuttled years ago under the Obama administration, only to find new life under President Trump. But opposition, from Alaska Native American communities, environmentalists and the fishing industry never diminished, and recently even the president’s son, Donald Trump Jr., a sportsman who had fished in the region, came out against the project.

On Wednesday, it failed to obtain a critical permit required under the federal Clean Water Act that was considered a must for it to proceed. In a statement, the Army Corps’ Alaska District Commander, Col. Damon Delarosa, said the mine, proposed for a remote tundra region about 200 miles from Anchorage, would be “contrary to the public interest” because “it does not comply with Clean Water Act guidelines.”

Opponents said the large open-pit operation, which would dig up and process tens of millions of tons of rock a year, would irreversibly harm breeding grounds for salmon that are the basis for a sports-fishing industry and a large commercial fishery in Bristol Bay. Salmon are also a major subsistence food of Alaska Natives who live in small villages across the region.

“The Corps’ denial of the permit for the Pebble Mine is a victory for common sense,” said Chris Wood, chief executive of the conservation group Trout Unlimited. “Bristol Bay is the wrong place for industrial scale mining.”

Lindsay Layland, deputy director of United Tribes of Bristol Bay, which has fought the project for years, said that while the decision means the project may be dead, the threat remains that the gold and copper ore could still be mined in the future. “It doesn’t mean that those minerals aren’t going to be in the ground tomorrow,” she said. “We need to continue to push for long term and permanent protections down the road.”

In a statement, John Shively, interim chief executive of the project’s developer, Pebble Limited Partnership, said the partnership would “focus on sorting out next steps for the project, including an appeal of the decision.”

Mr. Shively described the Corps’ action as “politically driven,” particularly given that earlier this year the Corps had approved an environmental impact statement that, he said, “clearly stated the project could successfully coexist with the fishery and would have provided substantial economic benefit.”

The environmental impact statement was finalized in July by the Corps, which had authority to approve or deny a permit under the federal Clean Water Act. But a few weeks later the Corps said that the company’s plan to compensate for environmental damage from the mine was insufficient, and requested a new plan.

The new plan, which was not publicly released but was believed to designate land near the mine to be permanently protected, was submitted last week.

The mining industry and many state officials have supported the project for the revenue and other economic benefits it would bring. But some important Alaskan politicians, notably Senator Lisa Murkowski, a Republican, had been noncommittal, saying the mine should go forward only if it could be shown to be environmentally sound.

In a statement on Wednesday, Senator Murkowski said the Corps’ decision affirmed “that this is the wrong mine in the wrong place.”

“This is the right decision, reached the right way,” she added.

Under the Trump administration, the Environmental Protection Agency reversed an earlier ruling, allowing the environmental review by the Corps to proceed. Under the Clean Water Act, the Corps reviews any dredging and filling activities in waterways, including wetlands like those in the area of the proposed project.

Support for the mine among Republicans was never as ironclad as it has been for some other projects with potential environmental consequences, notably potential oil and gas drilling in the Arctic National Wildlife Refuge, also in Alaska. And many Democrats had been fiercely opposed.

One of the project’s biggest Congressional critics, Senator Maria Cantwell, Democrat of Washington, hailed the Corps’ decision. “But denial of a permit does not mean Bristol Bay is safe from the threat of the Pebble Mine,” Senator Cantwell said, adding that the incoming administration of President-elect Joseph R. Biden Jr. should make it a priority to establish permanent protections for the Bristol Bay fishery.

The Pebble project even generated a rare dispute within the Trump family. In August, Donald Trump Jr., an avid sportsman who has fished in the Bristol Bay area, tweeted his opposition to the mine: “The headwaters of Bristol Bay and the surrounding fishery are too unique and fragile to take any chances with. #PebbleMine.”

President Trump, when asked in following days about his son’s sentiments and the prospects for the project, said only that he would “look at both sides” of the issue and that politics would not play a role in any decision. Privately, however, administration officials said they expected that the permit would be approved.

But in September, the future of the multibillion dollar project appeared in doubt when secret recordings of company executives suggested that they were planning for a much larger mine, and one that would operate far longer, than what had been proposed to the Corps.

The recordings were obtained by an environmental advocacy group, with two members who were posing as potential investors in the project meeting by video with two project executives. The executives described how the mine could operate for 160 years or more beyond the proposed 20 years, and how its output could double after the first two decades.

In the fallout from the recordings, one of the executives, Tom Collier, chief executive of the Pebble Partnership, resigned.