Last Updated Nov 22, 2022, 11:30 AM

San Francisco 49ers vs. Arizona Cardinals Picks, Predictions, Odds

Week 11 of the NFL season will conclude on Monday night with an NFC West rivalry between the San Francisco 49ers and Arizona Cardinals. Coverage begins from Estadio Azteca in Mexico City at 8:15 p.m. ET on ESPN.


Arizona is having an incredibly disappointing campaign, as the Cardinals stumbled out to a miserable 3-6 start to the season, and they appeared to be dead to rights following Kyler Murray’s hamstring injury against Seattle in Week 9.

However, a glimmer of hope arose in the form of the Cardinals’ defense alongside backup QB Colt McCoy this past Sunday, as Arizona posted a commanding 27-17 victory over the Rams in Week 10, while holding Sean McVay’s squad to just 256 total yards and forcing two turnovers in their previous contest.  

San Francisco is also having a bumpy campaign, but not nearly as bumpy as Arizona, as the Niners currently trail Seattle by half-a-game in the NFC West standings with a record of 5-4.

A handful of injuries derailed the operation for a brief moment, as San Francisco surrendered 28+ PTS in back-to-back losses to Atlanta and Kansas City in Weeks 6 and 7. But aside from those two games, their defense has been phenomenal this season, highlighted by the Niners smothering their opponents to 13.1 PPG across their other seven affairs.

I doubt we’ll see Arizona’s offense find much traction against an elite Niners unit on Monday night, regardless of who’s under center. But I also think we’ll see Jimmy Garoppolo and co. struggle a little bit on the road against a Cards’ defense that’s allowed 20 PTS or less in five of their last eight games. So, I’ll take the under here.

Score Prediction: 49ers 23, Cardinals 17
Best Bet: Under 43.5 (-110)


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Date: Monday, November 21, 2022
Matchup: NFC West
Venue: Estadio Azteca
Location: Mexico City
Time-TV: ESPN, 8:15 p.m. ET


The Niners stumbled out to a surprisingly slow start with Trey Lance under center, as San Francisco scored just 10 points on 331 total yards in a wild slip-and-slide game against Chicago in Week 1, which was followed by another weak performance out of the gate against Seattle in Week 2, as 21 of their 27 points came after Garoppolo’s entry in the first half.

San Francisco’s defense absolutely dominated the first five weeks of the year, as the Niners allowed just 12.2 PPG on 249 YPG across a solid 3-2 start to the season. However, their health issues caught up with them for a little while, as San Francisco surrendered 36 PPG across consecutive losses to the Falcons and Chiefs in Weeks 6 and 7.

Everything appears to be back in order now, though, as the Niners bounced back with a pair of stellar defensive performances against the Rams and Chargers in their latest two affairs, while holding their intrastate rivals to an average of 15 PPG in those contests.

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The Cardinals are 7-1-1 ATS in their last nine games against San Francisco. (Getty)


As of Saturday afternoon, Murray is listed as questionable for Monday’s contest with a hamstring injury. But if he’s actually healthy, and this is all just part of Kliff Kingsbury’s chess match, the under might be a tough sell here.

However, assuming that Murray isn’t quite at full strength, or McCoy gets the start, this is a brutal spot for Arizona hosting a Niners defense that’s allowed 16 PTS or less in six of their last eight games, a squad that’s pedal to the metal with its sights set on besting Seattle for the NFC West crown.

Kingsbury knows what he’s up against. In order to escape with a victory here, the Cardinals need to control time of possession with a defensive minded game script and keep the game within striking distance.

I doubt they’ll be able to pull off the upset, but at the very least, I trust their defense to keep things somewhat competitive in what’s essentially a must-win game if they want to keep their playoff hopes alive.


  • The Niners are 13-7 ATS in their last 20 games.
  • The total has gone UNDER in 13 of San Francisco's last 17 games.
  • The Niners are 4-2 SU in their last six games.
  • The total has gone OVER in four of Arizona's last five games.
  • The Cardinals are 5-11 SU in their last 16 games.
  • The Cardinals are 1-9 SU in their last 10 home games.
  • The Niners are 1-7-1 ATS in their last nine games against Arizona.
  • The Niners are 3-11 SU in their last 14 games against Arizona.
  • The total has gone UNDER in six of San Francisco's last eight road games.
  • The total has gone UNDER in five of San Francisco's last six road games against Arizona.
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