49ers vs. Cardinals Week 11 Prediction & Picks: Can Arizona win in Mexico City without Murray?

By | November 16, 2022

For the first time since 2019, we’ll have some NFL action in Mexico City this week as the San Francisco 49ers meet the Arizona Cardinals at Estadio Azteca in Week 11’s Monday Night Football matchup.

This NFC West rivalry showdown will be the NFL International Series game played in Mexico City, following games in 2016 (Texans vs Raiders), 2017 (Patriots vs Raiders), and 2019 (Chiefs vs Chargers).

Both teams will make the trip to Mexico City following wins over L.A.’s NFL teams in Week 10.

The Cardinals, with veteran QB Colt McCoy starting in place of the injured Kyler Murray (hamstring), topped the Matt Stafford-less Rams at SoFi Stadium, while the Niners came from behind to beat the Chargers at home.

It’s not yet known if Murray will be back in action against San Francisco. But how much of a consideration will that uncertainty be for my 49ers vs Cardinals prediction? Read on to find out.

San Francisco 49ers vs Arizona Cardinals Matchup Information and Betting Odds

Matchup Information

  • Matchup: San Francisco 49ers (5-4, 2nd in the NFC West) vs Arizona Cardinals (4-6, 3rd in the NFC West)
  • Venue & Location: Estadio Azteca (Mexico City, Mexico)
  • Date: Monday, November 21, 2022
  • Game Time: 8:15 pm ET (7:15 pm local time)
  • How to Watch 49ers vs Cardinals: ESPN

49ers vs Cardinals Odds

Game odds are via FanDuel as of Wednesday, November 16, 2022, at 3:00 pm ET. Odds from our other recommended legal sports betting sites may also appear in this article.


  • San Francisco 49ers -8.5 (-105)
  • Arizona Cardinals +8.5 (-115)


  • Over 43.5 (-112)
  • Under 43.5 (-108)


  • San Francisco 49ers -360
  • Arizona Cardinals +290

No Murray, No Problem for Arizona?

It is only one game, and the Rams were struggling mightily this season even with Stafford.

But there is a lot to be said for how well the Cardinals played in their 27-17 win.

Firstly, it was Arizona’s third-best scoring performance this season, behind their 42 points against the Saints in Week 7 and 29 in their overtime win over the Raiders in Week 2.

McCoy wasn’t spectacular, but he completed 26 of 37 passes for 238 yards and a touchdown, and he and the team played a turnover-free game.

Also, the Cards allowed 17 or fewer points for just the third time this season, and they allowed just 256 total yards, which is the second-fewest yards that they have allowed this season (220 vs the Carolina Panthers in Week 4).

The 49ers are not in the same disarray that the reigning Super Bowl champions, and the Cardinals will have to replicate that performance and then some to win this game, with or without Murray.

While many won’t be siding with Arizona for their 49ers vs Cardinals picks if Murray is sidelined again, the Cards aren’t in a bad position with an experienced guy who is familiar with his personnel.

After all, McCoy did start three games last season after Murray suffered an ankle injury and went 2-1, including a 31-17 win at San Francisco in his first start in Week 9.

If McCoy does start, expect another productive game for both DeAndre Hopkins and Rondale Moore.

Hopkins had 10 catches (from 14 targets) for 98 yards, while Moore had nine catches (from 13 targets) for 94 yards, all of which were season highs for the former Purdue star.

Mitchell’s Return Boosts San Francisco

Christian McCaffrey had only 39 yards on 14 carries against the Chargers last Sunday, but it was still a good night for San Francisco’s ground game thanks to the return of Elijah Mitchell.

Mitchell suffered an MCL sprain in the season opener against the Chicago Bears and missed the last seven games after being placed on injured reserve. He returned to the field against the Bolts and ran for 89 yards on 18 carries.

Mitchell’s eventual return was why Jeff Wilson Jr. was expendable after the Niners acquired McCaffrey (much to the Miami Dolphins’ benefit).

He won’t be counted on to catch passes as much as McCaffrey, but having to deal with Mitchell, McCaffrey, and regular runs for Deebo Samuel–who had 27 yards on four carries against the Chargers, his most carries since Week 3–is going to frustrate and tire a lot of defenses.

The Cardinals rank 12th in the NFL in yards allowed per carry (4.4). That is respectable, but it won’t strike the least bit of fear into the 49ers.

San Francisco 49ers vs Arizona Cardinals Prediction and Picks

49ers vs Cardinals Prediction: 49ers to win

49ers vs Cardinals Picks: 49ers/Cardinals 1st half over (Best Value: over 21.5 @ -108 at BetRivers) & Cardinals 1st half team total over (Best Value: over 7.5 @ +100 at BetRivers)

While I’m all in on the designated visiting team for my 49ers vs Cardinals prediction, I do think that the Cards can keep things competitive even if Murray misses a second straight game.

You never really know what you’re going to get with the Niners. They can look like a potential Super Bowl team one half then look like a completely different team the next. Or vice versa.

So, I absolutely do not feel comfortable with backing the cover for any of my 49ers vs Cardinals picks. However, I do see a lot of value in the totals, especially first half totals.

The 49ers have given up at least 14 points in the first half in each of their last four games: 21 vs the Falcons, 14 vs the Chiefs, 14 vs the Rams, and 16 vs the Chargers.

I don’t think the Cardinals will be the only team putting up points in the first half, and with that in mind, anything in that 20 to 24-point range is a play for me.

Other 49ers vs Cardinals Content at Betting News

  • 49ers vs Cardinals Consensus Picks, Score Projections, Betting Stats

Other NFL Week 11 Content at Betting News

  • NFL Week 11 Odds
  • NFL Week 11 Picks
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  • Eagles vs Colts Prediction & Picks
  • Bengals vs Steelers Prediction & Picks
  • Raiders vs Broncos Prediction & Picks
  • Cowboys vs Vikings Prediction & Picks
  • Chiefs vs Chargers Prediction & Picks (Week 11 Sunday Night Football)

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