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49ers vs. Cardinals Computer Picks, NFL Odds and Prediction for Monday Night Football on November 21, 2022
It'll be a bit of a different setting for this week's Monday Night Football game, as the San Francisco 49ers and Arizona Cardinals will clash at Estadio Azteca in Mexico City at 8:15PM ET on November 21.
Find out how we think this one will play out in our 49ers vs. Cardinals betting preview.
If you haven't already, you should consider signing up for DraftKings ➡️ here ⬅️ as you can turn a $5 pre-game moneyline bet on any game into a free $200 if your team wins.
49ers vs. Cardinals Computer Picks
Predictive Analytics Data
- No edge on either team to cover the 8-point spread
- 78% chance the 49ers win on the moneyline
- 56% chance 49ers-Cardinals goes Over 43.5
For the best NFL computer picks, check out our 49ers vs. Cardinals data predictions. They are constantly updating based on hundreds of different data points.
49ers vs. Cardinals Odds and Betting Lines
Why 49ers Will Cover The Spread
While neither of these teams has been a model of consistency, the Niners have much more going for them these days. Their offense added a huge piece in the form of Christian McCaffrey and is healthy from top-to-bottom — a rarity for this deep into the season.
San Francisco is 3-0 in divisional games so far and bringing the best defense in the NFL to Mexico City. Nick Bosa has 9.5 sacks, Talanoa Hufanga has four interceptions, and linebackers Fred Warner (69 tackles) and Dre Greenlaw (65) thrive against the run.
Arizona’s offense is in flux with Kyler Murray and Colt McCoy unlikely to get a full week of first-team reps, and tight end Zach Ertz done for the season with a knee injury.
Why Cardinals Will Cover The Spread
If Murray sits and McCoy retains the keys to offense, game management becomes much more vital for Arizona to hang tight. That means McCoy can’t turn the ball over, and the Cardinals’ ninth-ranked run defense can’t let McCaffrey and Elijah Mitchell carve out too many yards on the ground.
Arizona does have three straight-up wins as a road underdog so far. Although this is technically considered a ‘home’ game, the concept still fits.
Why The Over Will Hit
A healthy Murray would go a long way in reaching this total, but it remains to be seen if he can be 100 percent and the usual dual-threat. He passed for a combined five touchdowns in his last two starts despite suffering nine sacks. Murray also went for 60 yards rushing two weeks ago before injuring his hammy.
A lot of pundits believe the Niners are just beginning to get going offensively following last month’s addition of McCaffrey. They’re averaging 360.0 yards per game, good for ninth in the league.
Why The Under Will Hit
Yards aren’t easy to come by against San Francisco. The 49ers defense ranks No. 1 in the NFL in total defense (280.6 yards per game) as well as rushing defense (82.7 yards per game).
McCoy played well against the Rams, but midway through the season the Niners are proving to boast a much stronger defense than the defending champs. San Francisco also has 29 sacks, and opposing quarterbacks have a collective rating of only 84.9.
49ers vs. Cardinals Prediction
Lean: 49ers -8
Keep an eye on the injury report. Murray’s status will affect both the spread and total. Even so, he’s thrown for 300 yards just twice in nine games and the Niners are just beginning to pick up some steam.
Tony Bellissimo, with over 25 years of sports reporting and editing experience, has earned multiple New York State Press Association awards and oversees sports coverage for 30 high schools and several colleges on Long Island.
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