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49ers vs. Cardinals prediction: Back Arizona as a big underdog in Mexico City

San Francisco is laying too many points against NFC West rival on Monday Night Football

Arizona Cardinals quarterback Colt McCoy throws a pass against the San Francisco 49ers during a game last season. McCoy will start for the injured Kyler Murray when the Cardinals face the 49ers in Mexico City on Monday Night Football. (Photo by Ezra Shaw/Getty Images)
Arizona Cardinals quarterback Colt McCoy throws a pass against the San Francisco 49ers during a game last season. McCoy will start for the injured Kyler Murray when the Cardinals face the 49ers in Mexico City on Monday Night Football. (Photo by Ezra Shaw/Getty Images)Read moreEzra Shaw / Getty Images

The San Francisco 49ers are 1-3 this season outside the state of California — and that one win was against arguably the NFL’s worst team (Carolina).

Yet the 49ers headed south to Mexico City as the second-biggest favorite in Week 11 — against an NFC West foe that has beaten San Francisco 12 times in the last 16 meetings. That includes a sweep of last season’s series.

Why is the NFL betting marketplace so bullish on San Francisco heading into 49ers vs. Rams at Estadio Azteca? Mostly because Arizona is going with its backup quarterback. Another reason the 49ers are a big Monday Night Football favorite: Despite its mediocre 5-4 record, they entered Week 11 as the second choice (behind the Eagles) to win the NFC and are among a handful of Super Bowl favorites.

But that doesn’t mean San Francisco will cover this hefty Monday Night Football point spread at a neutral site. Here’s how we’re betting 49ers vs. Cardinals.

Note: Odds updated as of 10:30 a.m. on Nov. 21.

49ers vs. Cardinals Prediction: Pick

  1. Cardinals +10 (at BetMGM)

49ers vs. Cardinals Prediction: Analysis

San Francisco is grossly overvalued in this matchup — which is a statement you can make about this team nearly every week.

Yes, the 49ers are coming off consecutive wins over the Rams (31-14 on the road) and Chargers (22-16 at home). But the Rams (3-7) are a mess, and San Francisco managed just two touchdowns in five red zone trips against the Chargers last Sunday night — which is why the Niners failed to cash as an 8-point favorite.

Covering numbers has been an issue for San Francisco all season. It is 4-5 ATS, coming up short in three of the last four.

The 49ers are also 3-4 ATS as a favorite overall and 1-3 ATS as a favorite away from Levi’s Stadium. And as you might imagine for a team that’s 5-4 SU, they haven’t won three straight games this season.

In fact, San Francisco has had just one three-game SU winning streak (last November) since the middle of the 2019 season, when it went to the Super Bowl.

Will the 49ers record their second three-game winning streak in three years on Monday in Mexico City? They absolutely should.

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They field the NFL’s best defense. Their offense has three versatile weapons in running back Christian McCaffrey, wide receiver/running back Deebo Samuel and wideout Brandon Aiyuk. And they’re facing an average (at best) Cardinals team without its starting quarterback.

Kyler Murray, who missed last week’s game at the Rams with a hamstring injury, had been listed as a game-time decision throughout the week. But it was reported early Monday that Murray will sit out again.

That leaves the Cardinals’ offense in the hands of backup Colt McCoy. The ex-49er is dealing with his own injury, as he tweaked his knee late in the team’s 27-17 upset victory at the Rams in Week 10.

McCoy was limited in practice this week but will be under center in Mexico City. The betting market reacted to the Murray out/McCoy in news by moving this point spread from San Francisco -8 to -10, but we think that was an overreaction.

No doubt Murray is a far more dangerous playmaker, but he’s also more of a risk-taker — something you don’t want against the kind of fierce, opportunistic defense San Francisco fields.

Conversely, McCoy is a veteran signal-caller who knows how to manage a game and avoid soul-crushing mistakes. He showed that in San Francisco last season when he started for the injured Murray and went 22-for-25 for 249 yards with one touchdown and no turnovers in a 31-17 upset victory.

» READ MORE: Full sports betting coverage from The Philadelphia Inquirer

Back to San Francisco’s offense quickly: With Jimmy Garoppolo running the show, the 49ers rank ninth total offense but just 18th in scoring, averaging 22 points per game.

Why? Because they struggle in the red zone, as we saw multiple times against the Chargers. San Francisco has a 54.8% TD conversion rate inside the 20-yard line. That’s not only barely league average (16th), it’s below Arizona (60%, 9th).

So while the talent-rich 49ers should win this game, we wouldn’t be shocked if they didn’t. And neither would the Cardinals and their fans.

As previously noted, Arizona has owned this rivalry the past eight years. In addition to going 12-4 SU against San Francisco since the 2014-15 season, the Cardinals are 11-4-1 ATS. That includes a 5-0-1 ATS mark as an underdog. (Arizona is also 4-2 ATS as a dog this season.)

In fact, since a 32-20 home victory on Oct. 13, 2013, the 49ers have just one victory against the Cardinals by more than eight points.

So even though San Francisco is clearly the superior team and Arizona is down to its backup quarterback, we’re taking the generous points BetMGM is offering — especially since double-digit underdogs are 5-0 ATS the last four weeks.

49ers vs. Cardinals Odds (via FanDuel):

  1. Moneyline/Point spread: 49ers (-10) @ Cardinals (+10)

  2. Run line/moneyline: 49ers (-450) @ Cardinals (+340)

  3. Total: 42.5 points

The Inquirer is not an online gambling operator, or a gambling site. We provide this information about sports betting for entertainment purposes only.