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Since the San Francisco 49ers traded for Christian McCaffrey, they’re 2-1. The Arizona Cardinals, on the other hand, just snapped their two-game skid. Kade Kimble previews the Week 11 matchup and makes his pick.

Arizona Cardinals vs. San Francisco 49ers Prediction, Pick, Odds: Can the 49ers Dominate on MNF?

Since the San Francisco 49ers traded for Christian McCaffrey, they’re 2-1. The Arizona Cardinals, on the other hand, just snapped their two-game skid. They’re 4-6 on the NFL season compared to the 49ers' 5-4 record. Let’s take a look ahead of this NFL Week 11 matchup.

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49ers vs. Cardinals Start Time, Where to Watch

  • Date: November 21, 2022
  • Game Time: 8:15 pm ET
  • Where to Watch: ESPN

49ers vs. Cardinals Odds

  • Spread: 49ers -8 (-110), Cardinals +8 (-105)
  • Total: Over 43.5 (-109), Under 43.5 (-110)
  • Moneyline: 49ers (-350), Cardinals (+300)

Click here for 49ers vs Cardinals odds

Arizona Cardinals vs. San Francisco 49ers Prediction

First and foremost, the 49ers' defense is going to be a big point of emphasis looking at this game. They’re the best defense in the league by about 10 yards per game. They’re also the best-run defense in the league, so they’ll have the upper hand against the Cardinals' run game, which has Kyler Murray. 

The Cardinals should be forced into the passing game, which the 49ers are still solid at covering, as they’re 8th in the league in that department. Outside of the 49ers' two slip-ups defensively, they’ve been solid at limiting their opponents to under 20 points in their matchups. 

Recently, the Cardinals' offense has been improved, but they still struggle to put first-quarter points on the board, and the 49ers' defense will expose that weakness. Kyler Murray is questionable for the game as of now, but that could change as we get closer to the game. On the season, he has 2,168 passing yards with 12 touchdowns and six interceptions. He’s also the main source of their run game, as he leads the team with 359 rushing yards while tacking on two rushing touchdowns.

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It’s safe to say that the 49ers' defense should know where to target the Cardinals' offense, and if they hold them under 20 points, they should come away with a win. The Cardinals’ best weapon has been Marquise Brown, who’s been injured for the past month. 

The 49ers' offense is averaging 22 points per game this season, and they’ve got the tools to continue building on that front. They’ve got McCaffrey now, who can string together some huge games that can carry the offense. They’ve also got Deebo Samuel, who’s another great creator. 

Weapons aren’t something the 49ers lack, and they’re slowly putting together a very solid season with them, but Jimmy Garoppolo is going to have to find ways to convert that into points. 

Luckily for the 49ers, the Cardinals aren’t too solid at defense, as they rank in the bottom half of the league in that department. The 49ers' skill players should be able to string together some big plays. Again, Murray might not play, and he might not be fully healthy if he does, so the 49ers' offense might not require too many points to win. 

The 49ers' roster looks like a team that could contend for the Super Bowl, whereas the Cardinals have holes they need to clean up before they’re ready to take the next step. The 49ers didn’t have a hot start to this season, either, though. They need to string together some big games to prove their talent, and none better than a prime-time big win over the Cardinals.

The 49ers are eight-point favorites over the Cardinals, and even with Murray playing in this game, I like the 49ers to cover. The Cardinals' offense just hasn’t looked right this season, and it’s hard to imagine they’ll figure it out against a top defense in the league. The 49ers are 4-5 ATS, whereas the Cardinals are 5-5 ATS, so this matchup feels quite even.

Arizona Cardinals vs. San Francisco 49ers Pick

Article Author


Kade has spent his last 3 years writing about the Oklahoma City Thunder. He has also been following the NBA for the past 11 years. Just recently, Kade began co-hosting the Boomtown Hoops Podcast.


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