The new deal will run until 2030, averting the threat of a work stoppage at the end of the coming season and setting up a decade of labour peace, but it only just gained approval as 51.5 per cent of players voted in favour.
"NFL players have voted to approve ratification of the new collective bargaining agreement by a vote tally of 1,019 to 959," a statement from the NFL Players' Association said.
NFL commissioner Roger Goodell welcomed the deal.
"We are pleased that the players have voted to ratify the proposed new CBA, which will provide substantial benefits to all current and retired players, increase jobs, ensure continued progress on player safety, and give our fans more and better football," he said in a statement.
The deal, coming one day before free agency opens for the coming season, allows for the league to add a 17th regular season game from 2021, while the play-off field will be expanded from 12 to 14 teams from 2020.
The players' cut of the league's total revenue will rise from 47 per cent to 48 per cent, and could expand further if the NFL's broadcasting deals increase in value with the addition of a 17th game.
The deal also sees the NFL's minimum salary rise from 585,000 US dollars to 675,000 US dollars from next season, as well as an increase in the NFL roster from 53 to 55 players.
The existing collective bargaining agreement was due to expire at the end of the 2020 season.
NFL owners had approved the deal last month, while around 2,500 players had a 10-day voting period - ending at midnight on Saturday - in which they got their say.
Several high-profile players, including Aaron Rodgers, JJ Watt and Russell Wilson, had voiced their opposition, but the provisions for the minimum salary and the expansion of rosters was popular with those at the other end of the scale.
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