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49ers will play the Cardinals at Estadio Azteca in Mexico City on Nov 21.
— Adam Schefter (@AdamSchefter) May 4, 2022
Estadio Azteca is also the location of the league's first regular-season game outside the United States, which took place on October 2, 2005, and saw the Cardinals beat the 49ers 31-14.
There will be five total international games in 2022, with the New Orleans Saints, Green Bay Packers, Jacksonville Jaguars, Tampa Bay Buccaneers, and Arizona Cardinals serving as the "home teams." Below is the information for each matchup.
Minnesota Vikings vs New Orleans Saints
Tottenham Hotspur Stadium, United Kingdom (London)
October 2, 6:30 am PT, NFL Network
New York Giants vs Green Bay Packers
Tottenham Hotspur Stadium, United Kingdom (London)
October 9, 6:30 am PT, NFL Network
Wembley Stadium, United Kingdom (London)
October 30, 6:30 am PT, ESPN+
Seattle Seahawks vs Tampa Bay Buccaneers
FC Bayern Munich Stadium, Germany (Munich)
November 13, 6:30 am PT, NFL Network
San Francisco 49ers vs Arizona Cardinals
Estadio Azteca, Mexico (Mexico City)
November 21, 5:00 pm PT, ESPN
The 49ers last took part in an international regular-season game on October 27, 2013, when the team beat the designated home team Jacksonville Jaguars 42-10 at Wembley Stadium. Before that, they knocked off the designated road team Denver Broncos 24-16 at Wembley Stadium on October 31, 2010.
The NFL will release the remainder of the league schedule on May 12.
Last year, as part of the League's expansion of the regular season to 17 games, it was determined that, beginning with the 2022 season, up to four of the teams from the conference whose teams were eligible for a ninth regular-season home game would instead be designated to play a neutral-site international game each year.
This year's international series will kick off with games on back-to-back weekends at Tottenham Hotspur Stadium in London.
The New Orleans Saints and Minnesota Vikings will each play in the UK for the third time. Both teams have won on two previous occasions in the UK and will make their debut at Tottenham Hotspur Stadium on Sunday, October 2.
The following Sunday, October 9, the Green Bay Packers, NFC North champions for the third consecutive year, will face the New York Giants in their first international trip, becoming the 32nd NFL team to play in London since 2007. The Giants will play in the UK for the third time, having won the inaugural London game at Wembley Stadium in 2007 and also won the first game played at Twickenham Stadium in 2016. This will be their first game at Tottenham Hotspur Stadium.
In the first-ever NFL regular-season game in Germany, the two-time Super Bowl champion and current NFC South champion Tampa Bay Buccaneers, led by quarterback Tom Brady, will face the Seattle Seahawks on Sunday, November 13. As previously announced, Munich and Frankfurt were chosen to stage regular-season games in Germany over the next four years. The first game will take place at FC Bayern Munich Stadium.
The NFL will return to Mexico City on November 21 with Monday Night Football. Estadio Azteca will host a matchup between NFC West rivals San Francisco 49ers and Arizona Cardinals in a rematch of the NFL's first regular-season game played outside the United States. In 2005, the teams played at Estadio Azteca with 103,467 fans in attendance, the eight largest crowd in NFL history.
