The deal followed confidential negotiations ordered last month by U.S. District Judge Anita B. Brody in Philadelphia. Brody had been overseeing a wave of lawsuits brought by more than 4,500 former players, but lawyers said she had pressed them from the start to settle.
"This agreement lets us help those who need it most and continue our work to make the game safer for current and future players," NFL executive vice president Jeffrey Pash said in a statement. "Commissioner [Roger] Goodell and every owner gave the legal team the same direction: Do the right thing for the game and for the men who played it."
The league will also pay $75 million to cover baseline medical exams for retired players, $10 million for research into concussions and education about the dangers, and money to cover legal fees and a settlement administrator.
The NFL agreed to pay half the settlement within three years and the rest over the next 17, although it applies only to currently retired players.
The league admits no wrongdoing or liability.
Brody is expected to approve the agreement within 60 days, after a hearing to let any of the affected players object.
It is unclear if any will.
Some observers had said the players could have held out for a bigger amount from the NFL, but their lawyers said Thursday's settlement was the best and most efficient outcome because it avoided a costly legal war that could have dragged on for years.
"This is the only program where everybody gets justice," said Christopher Seeger of New York, one of the lead attorneys for the players.
As many as 18,000 former players will qualify for baseline medical tests. Those who are or already had been found to have concussion-related cognitive problems will get amounts determined by a third-party administrator.
The pact lasts 65 years, with a provision that the NFL will add to the fund if it dips below $50 million.
"It's a good deal, a fair deal," said Sol Weiss, the Philadelphia-based lawyer who represents about 250 former players, including former Eagles quarterback Jim McMahon.
Weiss said the settlement might mean more than $4 million for another client, the widow of Ray Easterling, a former Atlanta Falcons safety who killed himself last year and was found to have chronic traumatic encephalopathy (CTE), a degenerative brain disease linked to concussions.
The settlement calls for capping payouts of $5 million for players found to have Lou Gehrig's disease, $4 million for those who died of CTE, and $3 million for those with dementia.
The players had contended the NFL was supposed to be the guardian of their sport but instead hid the dangers of concussions while marketing and "mythologizing" the violence in the game. They sought damages for fraud and negligence and wanted the league to establish a court-supervised fund for the medical care of past and present players.
League officials denied any mass conspiracy, and instead portrayed the NFL as a vanguard in funding and responding to the mounting research of risks associated with head injuries.
The league also argued that individual teams and doctors, not the league, were responsible for decisions about a player's safety. And it claimed disputes related to player injuries are covered by its contract with the players' union, and belonged before an arbitrator, not in the courts.
But their challenge was as much a public-relations test as it was a legal one.
The roster of plaintiffs ranged from short-time benchwarmers to Hall of Fame heroes and Super Bowl MVPs from most every era, including running back Tony Dorsett, offensive lineman Forrest Gregg, quarterback Mark Rypien, and Junior Seau, a former linebacker who committed suicide in 2012.
Many did not specify their injuries, but instead filled out a seven-page template asserting they had played football and suffered concussions that had lasting impact.
Among the other former Eagles on the list are Bill Bergey, a popular Pro Bowl linebacker who anchored the team in the 1970s, and Dorsey Levens, a running back who played for the team in 2002 and 2004.
Lisa McHale, whose husband, Tom, was an offensive lineman for the Eagles in the 1990s and died in 2008 from a drug overdose, said she was surprised but thrilled that retired players and their families would soon get help.
McHale also called the settlement "a very public acknowledgment" by the NFL that it had not been an innocent bystander as evidence piled up about the risks of concussions.
"Clearly there was some wrongdoing," McHale, who lives in Tampa, Fla., said in a phone interview. "Clearly they were concerned about what would be disclosed" during the litigation.
Seeger would not say how far the process of sharing evidence had progressed or what lawyers expected to find. He said the two sides had talked nearly every day for more than a year, but that their negotiations grew more promising after Brody ordered them into mediation last month.
He praised the judge, who he said took an active role, and the mediator, former federal judge Layn Phillips, who coordinated several daylong negotiating sessions. The talks continued as late as 2 a.m. Thursday, he said.
Phillips was due to give Brody a report on the talks next week. Instead, he was able to report a settlement.
"This is a historic agreement, one that will make sure that former NFL players who need and deserve compensation will receive it, and that will promote safety for players at all levels of football," Phillips said in a statement.
On top of the deal, the NFL also agreed to pay players' legal fees in the case. It was not immediately clear how much that will be.
Stephen F. Ross, director of director the Penn State Institute for Sports Law, said he was not surprised by the settlement.
"In this particular case," Ross said, "you've got a huge PR issue as well for the National Football League - and they really want to move past it."
Contact John P. Martin at 215-925-2649, at firstname.lastname@example.org, or @JPMartinInky on Twitter.