The plaintiffs include at least 10 members of the Pro Football Hall of Fame, including former Dallas Cowboys running back Tony Dorsett. They also include Super Bowl-winning quarterback Jim McMahon and the family of Pro Bowl linebacker Junior Seau, who committed suicide last year.
Many former players with neurological conditions believe their problems stem from on-field concussions. The lawsuits accused the league of hiding known risks of concussions for decades to return players to games and protect its image.
The NFL has denied any wrongdoing and has insisted that safety has always been a top priority.
Senior U.S. District Judge Anita Brody in Philadelphia announced the proposed settlement Thursday after months of court-ordered mediation. She still must approve it at a later date.
The settlement likely means the NFL won't have to disclose internal files about what it knew, when, about concussion-linked brain problems. Lawyers had been eager to learn, for instance, about the workings of the league's Mild Traumatic Brain Injury Committee, which was led for more than a decade by a rheumatologist.
In court arguments in April, NFL lawyer Paul Clement asked Brody to dismiss the lawsuits and send them to arbitration under terms of the players' contract. He said that individual teams bear the chief responsibility for health and safety under the collective bargaining agreement, along with the players' union and the players themselves.
Players lawyer David Frederick accused the league of concealing studies linking concussions to neurological problems for decades.
Brody had initially planned to rule in July, but then delayed her ruling and ordered the two sides to meet to decide which plaintiffs, if any, had the right to sue. She also issued a gag order, so it has been unclear in recent weeks whether any progress was being made.
The lawyers were due to report back to her Tuesday, but Brody instead announced in court files Thursday that the case had settled.
In recent years, a string of former NFL players and other concussed athletes have been diagnosed after their deaths with chronic traumatic encephalopathy, or CTE. Those ex-players included Seau and lead plaintiff Ray Easterling, who filed the first suit in Philadelphia in August 2011 but later committed suicide.
About one-third of the league's 12,000 former players have joined the litigation since 2011. They include a few hundred "gap" players, who played during years when there was no labor contract in place, and were therefore considered likely to win the right to sue.