The N.F.L. suspended five players on Friday for violating the league’s gambling policy, including three who were banned for at least the entire 2023 season, in the biggest group of penalties for gambling violations in 60 years.

After a league investigation, receiver Quintez Cephus and safety C.J. Moore of the Detroit Lions and defensive end Shaka Toney of the Washington Commanders were suspended indefinitely for betting on N.F.L. games last season. The players can petition the league for reinstatement after the 2023 season.

Two other Lions players, receivers Stanley Berryhill and Jameson Williams, were each suspended for six games for other gambling violations, which the team said included betting from an N.F.L. facility on other sporting events.

The league declined to disclose specifics on the bets placed by these players or how the violations were uncovered, but said its investigation did not turn up evidence that “any inside information was used or that any game was compromised in any way.”

The penalties are effective immediately and are no longer subject to appeal, an N.F.L. spokesman said Friday.

Toney’s agent, Andy Simms, declined to comment when reached on Friday. Agents for the other four players and a representative for the N.F.L. players’ union did not respond to messages seeking comment.

Shortly after the suspensions were announced, the Lions cut Cephus, who spent parts of the past two seasons on injured reserve, and Moore, whom the team signed as an undrafted free agent in 2019.

“These players exhibited decision making that is not consistent with our organizational values and violates league rules,” Lions General Manager Brad Holmes said in a statement. The Commanders said in a statement that they “support the league’s findings and actions.” Toney remains on the team’s roster.

The penalties levied Friday follow those given to former Atlanta Falcons receiver Calvin Ridley, who received a season-long ban in 2022, and Arizona Cardinals defensive back Josh Shaw, who was suspended in November 2019 through the end of the 2020 season. Both players were punished for gambling on N.F.L. games.

The recent run of suspensions, the first in decades, comes after the N.F.L. reversed its long-held opposition to sports gambling. In 2017, team owners voted to approve the Raiders’ move to Las Vegas, and a major turning point came in 2018, when the Supreme Court struck down a 1992 law that banned sports wagering in nearly every state. Since then, the N.F.L. and other professional American leagues have forged partnerships with major gambling companies and casinos.

The last cluster of N.F.L. gambling penalties on the same scale as those announced Friday came in 1963, when the Green Bay Packers running back Paul Hornung and the Lions defensive lineman Alex Karras — then two of the league’s biggest stars — were suspended for the season for betting on N.F.L. games. Five other players were also fined for betting on the 1962 championship game.

N.F.L. Commissioner Roger Goodell did not comment on the suspensions issued Friday, but when Ridley’s ban was announced in 2022, he said N.F.L. personnel gambling on football games warranted “the most substantial sanction” because it risked the “integrity of the game.”

Specifics of the five players’ violations were not made public.

In Ridley’s case, he used a gambling app to place three parlay bets in November 2021 while he was in Florida and away from his team. Genius Sports, a company hired by the N.F.L. to provide “comprehensive integrity services to monitor betting,” alerted the N.F.L. that a player might have made the bets, triggering a league investigation.

An N.F.L. spokesman said each year the league informs personnel of policies that prohibit them from placing or facilitating bets on any N.F.L. game, practice or other event, such as the draft. Players are allowed to bet on other sports, but they may not gamble in the workplace or while working, which includes traveling to games or while making promotional appearances on the league’s behalf.