There will be a shoutout to history on Monday Night Football in Week 11. Over the last decade, we have seen dozens of NFL games played in different locales, but the very first regular season game played outside the United States occurred all the way back in 2005 when the Arizona Cardinals and San Francisco 49ers met at Estadio Azteca. San Francisco will draw level with the Seattle Seahawks in the NFC West race with a victory in this one. 

The last international game of the year will take place on Monday Night Football when the Arizona Cardinals and San Francisco 49ers square off on Monday, November 21, 2022, at Estadio Azteca in Mexico City, Mexico at 8:15 p.m. ET on ESPN.

San Francisco 49ers vs. Arizona Cardinals Betting Odds at BetRivers Sportsbook

San Francisco 49ers -8
Arizona Cardinals +8
Total 43.5

San Francisco 49ers vs. Arizona Cardinals Preview

Despite having a record of 5-4, the San Francisco 49ers have the second-lowest betting odds to win the Super Bowl in the NFC. San Francisco made arguably the biggest deal at the deadline, acquiring Christian McCaffrey from Carolina, and he should be superb in this offense. McCaffrey is one of the best receivers out of the backfield the league has ever seen, and that’s something that Kyle Shanahan covets for Jimmy Garoppolo in this offense. The Niners traded away Jeff Wilson Jr., but Elijah Mitchell is healthy once more, and he is averaging 5.4 YPC.

As for Garoppolo, he is simply asked to be a game manager in this offense. He is completing 66.8% of his passes for 1,931 yards (8.1 YPA) with 11 touchdowns and four interceptions. Brandon Aiyuk is currently the leading receiver, but the two players that are the most feared in the passing attack are Deebo Samuel and George Kittle.

Arizona’s defense is going to have a hard time stopping San Francisco’s ground game. The Cardinals rank 30^th in scoring defense (25.8 PPG), and they aren’t designed to stop a power run game up front. Inside linebackers Zaven Collins and Isaiah Simmons are speedy and solid in coverage, but they don’t get off their blocks well. Their pass rush has struggled after the departure of Chandler Jones this offseason, and J.J. Watt leads the team with 5.5 sacks.

The Cardinals may be in real trouble on offense too. Kyler Murray is questionable to play with a hamstring injury and has been limited in practice this week, and backup quarterback Colt McCoy has been limited with a knee injury. We’ve yet to hear any update to their status as of Friday morning, so there is a chance that third string QB Trace McSorley gets the start.

To make matters worse, those aren’t the only injuries that Arizona is dealing with on offense. The offensive line is extremely banged up with three players (two starters) on injured reserve, and D.J. Humphries and Max Garcia are both listed as questionable. Standout receiver DeAndre Hopkins was recently added to the injury report too, and that would be a huge loss considering Zach Ertz and Marquise Brown have already been ruled out with injuries.

San Francisco has the best defense in the NFL. The 49ers are allowing just 18.1 PPG and 280.6 YPG, and the front seven has been outstanding at stopping the run. They are allowing just 3.4 YPC (1^st in the NFL) and 82.7 YPG on the ground (2^nd in the NFL), and that’s despite Javon Kinlaw being on injured reserve for two months. Arik Armstead and Samson Ebukam have been excellent up front, while Nick Bosa is on his way to being named an All-Pro once more. Bosa has 9.5 sacks and 11 tackles for loss. Second-year safety Talanoa Hufanga is quickly becoming one of the best at his position too with four interceptions on the year.

San Francisco 49ers vs. Arizona Cardinals Prediction

This game has the potential to be a blowout, especially if Murray is unable to play for the Cardinals. San Francisco can grind down Arizona’s front seven, and the Cardinals could be gassed earlier than expected due to the elevation of Estadio Azteca. Look for the Niners to win this NFC West showdown by at least 10 points.