The San Francisco 49ers are scheduled to meet the Arizona Cardinals at 103,000-seat Estadio Azteca in Mexico City on Monday night to close out Week 11 of the 2022 NFL season.
The 49ers were listed as an 8-point favorite on look-ahead lines. The spread ranged from 8-8.5 points at DraftKings, FanDuel, BetMGM, and PointsBet during early wagering, and it’s up to 9.5 or 10 a few hours before kickoff. Some that movement is related to news that Kyler Murray is expected to miss his second straight game, and Colt McCoy will get the start.
This is the last game to be played outside the US this season.
Let’s take a look at the latest 49ers vs. Cardinals odds and a MNF prediction.
49ers vs. Cardinals Betting Line: Point Spread, Moneyline, Total
Here are 49ers vs. Cardinals odds from around the sports betting industry.
NFL · Mon (11/21) @ 8:15pm ET
SF 49ers | at | ARI Cardinals |
State Farm Stadium, Glendale, Arizona |
Cardinals Come Into MNF Banged Up
It was 17 years ago when the 49ers and Cardinals, a pair of teams that finished with double-digit losses, met in Estadio Azteca in the first NFL regular-season game outside the U.S. Arizona prevailed 31-14 as a 3-point favorite with Josh McCown throwing for 385 yards and two scores.
Now, San Francisco (5-4 overall, 4-5 ATS) is coming off a 22-16 victory over the LA Chargers as an 8-point pick last Sunday. The 49ers are a half game out of first in the NFC West entering Week 11 play. The 49ers are also a +900 choice at PointsBet to win the Super Bowl, the fourth betting favorite on the board.
The Cardinals (4-6 overall, 5-5 ATS) had lost four of five before defeating the Rams in Los Angeles 27-17 on Sunday in a battle between backup QBs. Arizona’s Colt McCoy filled in for Kyler Murray (hamstring), and LA went with John Wolford in place of Matthew Stafford (concussion protocol).
McCoy again is expected to start for Arizona, despite injuring a knee late vs. the Rams.
Listed as third on the Cardinals’ QB depth chart is well-rested Trace McSorley, who’s thrown 14 passes since being drafted in the sixth round by Baltimore in 2019.
Another question mark is whether Arizona WR Marquise Brown will play after missing the past four games with a foot injury. He worked on individual drills in practice Thursday. Despite his absence, he remains the Cardinals’ leading receiver with 485 yards.
Also, star TE Zach Ertz is out for the rest of the year after injuring his knee last week. He leads Arizona receivers with 47 receptions and four TDs. While we’re at it, WR DeAndre Hopkins is questionable with a hamstring injury.

San Francisco, meanwhile, is a far cry from how it looked early in the season when it didn’t yet trade for RB Christian McCaffrey, when star RB Elijah Mitchell was out for half the season with a knee injury, TE George Kittle was nursing an injury, pass-rush specialist Nick Bosa a missed a game, and All-Pro OLT Trent Williams was out.
They’re all back now, along with others, which is why they have odds of +900 (PointsBet) to win Super Bowl 57. Only three other teams are heavier favorites.
One more tidbit: The Cardinals could be in big trouble if they continue to commit so many penalties. In their past three games, they’ve had double-digit flags. No other team has done that in three straight outings this season.
Bet NFL sides at BetMGM: Use bonus code TODAY for a $1,000 risk-free bet
49ers vs. Cardinals Prediction
The 49ers went the extra mile in preparation to play at an elevation of 7,200 feet in Mexico City by conducting practices this week in Colorado Springs at an elevation of 6,700 feet. That should help late in the game when players are gasping for whatever air there is at that elevation.
Arizona, meanwhile, likely will be operating short-handed on the offensive line with starting center Rodney Hudson being put on IR this week (knee). Plus LT D.J. Humphries (questionable) still has a back issue that kept him out of last week’s game, and LG Max Garcia (questionable) has missed the past three with a shoulder injury.
This is not a time to be going up against the league’s top-ranked defense and a stadium filled with fans cheering on the 49ers even though it’s technically Arizona’s “home” game.
Forecast: 49ers 31, Cardinals 16
Also read: NFL Week 11 Betting Trends | NFL Week 11 Odds | Odds to make 2023 NFL playoffs