Major League Baseball has permanently banned Tucupita Marcano after determining that the infielder placed hundreds of bets on baseball, including wagers on games involving the Pittsburgh Pirates when he was with the team last season.

MLB said Tuesday that Marcano placed 387 baseball bets totaling more than $150,000 in October 2022 and from last July through November with a legal sportsbook. He became the first active player in a century banned for life because of gambling.

Marcano appears to be the first active major leaguer banned under the sport's gambling provision since New York Giants outfielder Jimmy O'Connell in 1924. Pete Rose, baseball's active career hits leader, famously agreed to a lifetime ban in 1989 after an investigation concluded he bet on Cincinnati Reds games while managing the team.

"The strict enforcement of Major League Baseball's rules and policies governing gambling conduct is a critical component of upholding our most important priority: protecting the integrity of our games for the fans," commissioner Rob Manfred said in a statement. "The longstanding prohibition against betting on Major League Baseball games by those in the sport has been a bedrock principle for over a century. We have been clear that the privilege of playing in baseball comes with a responsibility to refrain from engaging in certain types of behavior that are legal for other people."

Marcano, currently a member of the San Diego Padres, was found to have placed 231 MLB-related bets, including 25 that MLB says included wagers on Pirates games while he was on the team's major league roster. However, he did not appear in any of those games because he was on the injured list following a season-ending knee injury. He was receiving medical treatment at PNC Park during that time.

"We are extremely disappointed of Tucupita's actions and are fully supportive of Major League Baseball's ruling," the Pirates said Tuesday in a statement. "The Pirates, along with MLB, Players Association, and every Club, work to ensure all involved within our game are aware of the rules and policies around gambling. While the thorough investigation revealed no evidence of any games being compromised, influenced, or manipulated in any way in this case, protecting the integrity of our game is paramount."

Marcano bet almost exclusively on the outcomes of games and lost all of his parlay bets involving the Pirates, winning just 4.3% of all of his MLB-related bets, according to the league.

MLB Rule 21, posted in every clubhouse, states betting on any baseball game in which a player, umpire, league official or team employee has no duty to perform results in a one-year suspension. Betting on a game in which the person has a duty to perform results in a lifetime ban.

"We cannot comment on violations that occurred outside of our organization," the Padres said in a statement. "We fully support MLB's sports betting policy and the need to adhere to all provisions of Rule 21. We will continue to educate all members of our organization regarding their obligations under the policy."

One other big leaguer, Oakland Athletics pitcher Michael Kelly, was declared ineligible for one year on Tuesday for betting on baseball while he was in the minor leagues. Additionally, minor leaguers Jay Groome of San Diego, Jose Rodriguez of Philadelphia and Andrew Saalfrank of Arizona were banned for one year for betting on major league games.

MLB said it was tipped off about the betting activity by a legal sports betting operator. None of the players punished played in any games on which they wagered, and all players denied to MLB they had inside information relevant to their bets or the games they bet on -- testimonies that MLB says align with the data received from the sportsbook.

Marcano became the second North American athlete banned for gambling in recent months. The NBA gave Toronto's Jontay Porter a lifetime ban in April after concluding he disclosed confidential information to bettors and wagered on games, including on the Raptors to lose.

The other four players did not bet on games involving their assigned teams.

Kelly placed 10 bets on nine major league games from Oct. 5-17, 2021, while a minor league player assigned to Houston's Triple-A Sugar Land farm team. The bets included wagers on outcomes, over/under on runs and an individual pitcher's strikeout total. Three of the nine games involved the major league Astros. His wagers totaled $99.22 and resulted in $28.30 of winnings.

Kelly, 31, was 3-2 with a 2.59 ERA in 28 games this season, last pitching Saturday at Atlanta. The former first-round draft pick appeared in 46 games over the past three seasons.

Groome, a 25-year-old who had been on a minor league injured list since mid-April, placed 32 MLB-related bets from July 22, 2020, through July 24, 2021, including 24 on the Boston Red Sox major league team while he was assigned to Boston's High-A team in Greenville, South Carolina. The sport detailed he wagered $453.74 on 30 MLB games and had a net loss of $433.54, receiving payouts on only two wagers. His betting included parlays.

Rodríguez, 23, has been at Double-A Reading this season. He placed 31 bets on baseball on Sept. 30, 2021, and from June 5 through July 30 in 2022, including 28 on MLB and three on college baseball. The total included seven involving the Chicago White Sox at the time he was assigned to their Double-A team in Birmingham, Alabama. Two of the White Sox bets involved outcomes and the others were on runs scored. He bet $749.09 on baseball, of which $724.09 was on MLB-related bets that included parlays.

Saalfrank, 26, pitched in 21 games for Arizona last year between the regular season and postseason, including three World Series games, and two this year before he was optioned to Triple-A Reno on May 1. He placed 29 baseball bets from Sept. 9 through Oct. 29 in 2021 and on March 9, 2022, including 28 on MLB and one parlay on college baseball. He placed four bets on the big league Diamondbacks while on the injured list of their Low A farm team. His baseball bets totaled $445.87 on baseball, including $444.07 on MLB, and lost $272.64 on MLB bets and $1.80 on the college wager. He won just five of 28 MLB bets, which included outcomes, runs and pitcher strikeouts.

ESPN's Jeff Passan and The Associated Press contributed to this report.