U.S.-based Major League Baseball (MLB) called off opening day, effectively delaying the start of the regular season after it failed to reach a labor agreement with players by a Tuesday deadline.

The 2022 season was scheduled to begin with opening day on March 31.

"The calendar dictates that we're not going to be able to play the first two series of the regular season and those games are officially canceled," MLB Commissioner Rob Manfred told a press conference.

Service time toward free agency, playoff expansion, luxury tax and a salary floor are among key issues in the current dispute, which led the league to lock out the players in December.

"The clubs and our owners fully understand just how important it is to our millions of fans that we get the game on the field as soon as possible," Manfred said.

"To that end, we want to bargain and we want an agreement with the Players' Association as quickly as possible."

Players Association Executive Director Tony Clark said it was a sad day for the players, fans and the game and called the lockout the "ultimate economic weapon" to use against the players.

"In a $10 billion industry, the owners have made a conscious decision to use this weapon against the greatest asset they have: the players," Clark told a news conference.

"But the group won't be intimidated. I've seen more unity over the last few years than any time in our recent history," he said, adding that the group was committed to the bargaining process and getting back on the field as soon as possible.

The union has said throughout the talks it has sought to promote competition, provide fair compensation to young players and uphold the integrity of the market system for talent.

A handful of players criticized Manfred and the owners on social media after he spoke.

Talks break down

The breakdown in negotiations toward a new collective bargaining agreement came after the sides met for more than 16 hours Monday and again Tuesday in Jupiter, Florida, in an effort to avoid the first missed games due to a labor dispute since the players' strike of 1994-1995.

That work stoppage forced a premature end to one season, delayed the start of the next year's campaign and turned off fans, with attendances plummeting when play finally resumed.

MLB had previously said it would cancel games if a deal was not met by the end of the day on Monday, but the league said enough progress was made that it decided to push the deadline back to Tuesday.

The players union unanimously rejected MLB's last offer just before the deadline expired.

The canceled games will not be made up and the players will not be paid, Manfred said.

"We're prepared to continue negotiations," he said.

"We've been informed that the MLBPA is headed back to New York, meaning that no agreement is possible until at least Thursday. As such, camps could not meaningfully operate until at least March 8, leaving only 23 days before the scheduled opening day."

The league has said a month of spring training is needed to protect the health and safety of players.