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Estadio Azteca hosted a game every year from 2016 to 2019, save for the 2018 season when the Rams' clash with the Kansas City Chiefs was moved back to Los Angeles because of poor field conditions.
But the coronavirus pandemic meant there were no International Series games in 2020, with Mexico City left off the schedule for 2021.
It was confirmed in February that the Cardinals would host a game in Mexico City and it was announced on Wednesday that they will face their NFC West rivals on November 21.
Both the Cardinals and the Niners made the playoffs in 2021, Arizona losing in the Wild Card round to the eventual Super Bowl-champion Rams and San Francisco beaten by the same opposition in the NFC Championship Game.
The Cardinals and the Niners met in the first NFL game to be played in Mexico back in 2005, with Arizona claiming a 31-14 victory.