The San Francisco 49ers, a perfect 2-0 since adding Christian McCaffrey to the offense, head to Mexico City to face the Arizona Cardinals, who won last week with Colt McCoy and hope to do so again. 

The Niners (5-4) and Cardinals (4-6) are each looking up at the Seahawks (6-3) in the NFC West. Arizona has won three of the last four meetings, including both last year. Kyler Murray may miss this game again; McCoy is 4-2 in his last six starts, including last week’s 27-17 win over the Rams. 

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Oddsmakers at NFL betting sites aren’t giving the Cardinals much of a chance in Mexico. San Francisco is at -8 in the latest 49ers vs. Cardinals odds, while the total is 43.5 points. 

Bookies.com NFL handicapper Adam Thompson – who hit on 59.3% of his NFL best bets this season, and 62-64% of his NFL picks in each of the last three years – makes his selections for the NFC West showdown south of the border. 

49ers vs. Cardinals Point Spread Pick

Arizona has dominated against the spread against San Francisco of late, going 7-1-1 in the last nine meetings. The Cardinals have received points in almost all of them and do so again here. On the flip side, favorites on betting apps rule in international games, with a cover rate of 62.2%. 

San Francisco beat the Chargers by six last week but the score was an anomaly; the 49ers dominated. They should again here, up front and at the skill spots. The NFL’s top-ranked defense will put a new level of pressure on Colt McCoy compared to what he saw vs. the floundering Rams. SF has covered in five straight vs. divisional foes, and the favorite has covered in every game in Mexico City. Take the Niners and lay the eight points.

49ers vs. Cardinals Over/Under Best Bet

The 49ers rank No. 1 in the NFL in yards allowed and No. 4 in points. The offense has only garnered 22.5 ppg over the last four weeks and showed last week that it can, and will, run over everyone with Christian McCaffrey, Deebo Samuel and a now-healthy Elijah Mitchell. 

We’re not going to bank on McCoy or Kyler to get much done against San Francisco. With the Niners running clock, and the game in the altitude of Mexico City, the Under is our lean for Monday night. 

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49ers vs. Cardinals Moneyline Pick

San Francisco is -350 on the moneyline on sports betting sites, a steep price on any NFL team in a season full of straight-up upsets. Arizona, meanwhile, is +290. 

We’re not backing the Cardinals. The QB situation is murky, the 49ers defense is too strong and their lines are too overpowering for anyone to consider going with Arizona. We like San Francisco at this steep price, but the NFL 2022 season keeps us from going all-in. 

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Best 49ers vs. Cardinals Player Props

George Kittle, Over 41.5 Receiving Yards

Odds: -130 at DraftKings

Kittle has had a lighter presence in the Niners offense with Christian McCaffrey in the mix, with only 39 and 21 yards the last two weeks, this after generating 83 and 98 the two prior. But he’s surpassed this total in each of the last six meetings vs. Arizona. No team has allowed more yards to TEs in 2022 than the Cardinals. 

James Conner, Longest Reception Over 10.5 Yards

Odds: -125 at DraftKings

Conner has 22 receptions in seven games, only three of which have gone over 10 yards in distance. But the last three games he’s had several eight-yard receptions. Facing the NFL’s toughest run defense should mean fewer passes in the flat for Conner, especially in the absence of the other shorter-distance option, TE Zach Ertz. Conner has the skill to break one for 11-plus. 

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