49ers vs Cardinals Prediction: Week 11 Picks, Live Odds & Start Time – November 21, 2022

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The San Francisco 49ers (5-4) and Arizona Cardinals (4-6) travel to Mexico City, Mexico November 21, 2022 for a neutral-site contest at 8:15 PM ET, airing on ESPN.

49ers vs. Cardinals Odds

Point Spread

The spread for this matchup is set at 8.5 points, with bookmakers listing the 49ers as the favorites.


As for the moneyline, the 49ers have -390 odds to pick up the win, while the Cardinals are listed at +320 to claim victory.


Finally, the total for the game is set at 43 points.

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Game Info

How to Watch 49ers vs. Cardinals Live?

  • Game Day: Monday, November 21, 2022
  • Game Time: 8:15 PM ET
  • TV Channel: ESPN
  • Location: Mexico City, Mexico
  • Stadium: Estadio Azteca

Betting Preview


The 49ers own the ninth-ranked offense this season (360.0 yards per game), and they’ve been even better on the other side of the ball, ranking best with just 280.6 yards allowed per game. The 49ers own the 18th-ranked offense this season (22.0 points per game), and they’ve been better defensively, ranking fourth-best with just 18.1 points allowed per game.

The 49ers rank 10th in pass offense (236.3 passing yards per game) and eighth in pass defense (197.9 passing yards allowed per game) this year. Defensively, the 49ers have been a top-five unit in terms of rushing yards, ranking second-best by surrendering just 82.7 per game. They rank 13th on offense (123.7 rushing yards per game).

On the offensive side of the ball, the 49ers have been a top-five unit in terms of third-down efficiency, ranking fifth-best in the NFL by averaging a 45.6% third-down conversion rate. They rank 17th on defense (41.0% third-down percentage allowed). The 49ers have been a difficult matchup for opposing teams in terms of yards per play, as they rank top-five in both offensive yards per play (fifth-best with 5.9) and yards per play allowed on defense (third-best at 4.7) this year. The 49ers rank 25th in the league with a -3 turnover margin after forcing 10 turnovers (21st in the NFL) while committing 13 (18th in the NFL).


The Cardinals are compiling 333.7 total yards per contest on offense this season (19th-ranked). Meanwhile, they are surrendering 357.6 total yards per game (23rd-ranked). The Cardinals rank 13th in points per game (23.0), but they’ve been worse on the defensive side of the ball, ranking third-worst in the NFL with 25.8 points ceded per contest.

The Cardinals are posting 220.6 passing yards per game on offense this season (18th-ranked). Meanwhile, they are surrendering 247.1 passing yards per game (23rd-ranked) on defense. With 113.1 rushing yards per game on offense, the Cardinals rank 19th in the NFL. On defense they rank ninth, allowing 110.5 rushing yards per contest.

The Cardinals’ offense has been struggling on third down, ranking fifth-worst in the NFL with a 34.8% third-down conversion percentage. They have been more effective on the defensive side of the ball, allowing a 44.0% third-down rate (26th-ranked). The Cardinals’ offense has been sputtering in terms of yards per play, ranking fourth-worst in the NFL at 4.9. They have been better defensively, allowing 5.7 yards per play (20th-ranked). The Cardinals have compiled 14 forced turnovers this season and have turned it over nine times, leading to a +5 turnover margin, which ranks fifth-best in the NFL.

49ers vs. Cardinals Injury Report


Player Pos. Injury Status


Player Pos. Injury Status
Kyler Murray QB Hamstring Questionable
Marquise Brown WR Foot Questionable
Zach Ertz TE Leg Out
DeAndre Hopkins WR Hamstring Questionable
Byron Murphy CB Back Out

49ers vs. Cardinals Betting Analysis

49ers Betting Insights

The 49ers have covered the spread in a matchup four times this season (4-5-0). The 49ers are a perfect 1-0 ATS when playing as at least 8.5-point favorites.

This season, 49ers games have hit the over three times. The 49ers won 57.1% of the games last season when they were the moneyline favorite (8-6).

The 49ers won all three games they played as a moneyline favorite with odds of -390 or shorter.

Cardinals Betting Insights

The Cardinals have put together a 5-5-0 record against the spread this season.

Games involving Cardinals have hit the over five times this year. This season, the Cardinals have won three out of the seven games in which they’ve been the underdog.

The Cardinals have not entered a game this season with longer moneyline odds than +320.

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49ers vs. Cardinals Against The Spread & Betting Records


Overall Home Away
Point Total AVG 42.9 43.9 42.2
Implied Total AVG 23.2 24.0 22.6
ATS Record 4-5-0 2-2-0 2-3-0
Over/Under Record 3-6-0 1-3-0 2-3-0
Moneyline Favorite Record 4-3 3-0 1-3
Moneyline Underdog Record 1-1 0-1 1-0


Overall Home Away
Point Total AVG 47.8 48.8 46.7
Implied Total AVG 25.6 26.4 24.8
ATS Record 5-5-0 2-3-0 3-2-0
Over/Under Record 5-5-0 3-2-0 2-3-0
Moneyline Favorite Record 1-2 1-1 0-1
Moneyline Underdog Record 3-4 0-3 3-1

Players to Watch


  • Christian McCaffrey‘s rushing output this season includes 563 yards and four TDs. He is averaging 62.6 yards per game and 4.5 per attempt (32nd in the NFL).
  • He’s also hauled in 47 passes (on 59 targets) for 395 receiving yards with two touchdowns. He’s averaging 43.9 receving yards and 5.2 catches per game.
  • Jimmy Garoppolo has passed for 1,931 yards, 11 touchdowns and four interceptions this year. He is averaging 241.4 yards per game and 8.1 per attempt, while completing 66.8%.
  • He has rushed for 26 yards (sixth on the 49ers) and added two touchdowns on the ground, while averaging 3.3 rushing yards per game.
  • Brandon Aiyuk has four touchdown catches this season, and has 44 receptions for 567 yards on 61 targets, while averaging 4.9 catches and 63.0 yards per game.
  • Deebo Samuel has 34 catches for 411 yards and two touchdowns. He’s been targeted 61 times in the passing game, and averages 4.3 receptions and 51.4 yards through eight games played.
  • Over on defense, Nick Bosa has 26 tackles, 10.0 TFL, and 9.0 sacks in 2022.
  • Talanoa Hufanga has 50 tackles, 3.0 TFL, 1.0 sack, and four interceptions so far this season. He’s third on the 49ers in tackles.
  • Fred Warner has totaled 69 tackles, 3.0 TFL, 2.0 sacks, and six passes defended.
  • This season, Dre Greenlaw has 64 tackles and 2.0 TFL. He’s second on the 49ers in tackles.


  • Kyler Murray is averaging 6.0 passing yards per attempt (40th in the NFL) and 240.9 yards per game this year, completing 66.7% of his passes on the way to 2,168 total yards, 12 touchdowns and six interceptions through nine games.
  • He’s added 359 yards on the ground (first on the Cardinals), while scoring two rushing touchdowns. He’s averaging 39.9 yards per game and 6.1 per attempt.
  • Zach Ertz has 47 catches for 406 yards and four receiving touchdowns. He has been targeted 69 times and averages 4.7 receptions per game in 10 games played.
  • James Conner is averaging 44.9 rushing yards per game this season (314 total yards), while scoring three rushing touchdowns.
  • Conner’s statistic output includes 22 receptions (3.1 per game) on 27 targets for 139 yards (19.9 per game), but he has not scored a touchdown through the air.
  • DeAndre Hopkins has 36 catches for 396 yards and two receiving touchdowns. He averages 9.0 yards per game in four games and has been targeted 46 times.
  • In 2022, Zaven Collins has recorded 65 tackles, 4.0 TFL, 2.0 sacks, and one interception over 10 games.
  • Budda Baker’s stat sheet includes one interception as well as 75 tackles, 1.0 TFL, and three passes defended.
  • Isaiah Simmons has 2.0 sacks (third on the Cardinals) as well as 2.0 TFL, 49 tackles, and one interception in the 2022 campaign.
  • Jalen Thompson’s season stats include 60 tackles and one interception through 10 games. He is third on the Cardinals in tackles.

49ers vs. Cardinals Predictions and Pick

Our prediction to win this game is the 49ers, and we predict that Cardinals will cover the spread (49ers -8.5). Finally, we see the scoring in this one going over the posted total of 43 points.

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How to Bet on 49ers vs. Cardinals

You can bet on 49ers vs. Cardinals at every legal online sportsbook. For more NFL odds, including moneylines, spreads, over/under totals as well as NFL prop odds, check out the latest NFL lines as well as our guide to the best NFL betting sites.

And if you wanted to check out how much you could win on a $10 bet if you parlayed today’s 49ers vs. Cardinals picks, don’t forget to check out our free parlay calculator.

Not sure what a parlay is? Or even how to bet on football? Check out our complete guide to sports betting.


Brian Twining

Sports, of all kind, have been a huge part of my life and daily routine for as long as I can remember. My favorite sports to watch are College Basketball, College Football, the NFL, MLB, Nascar, & the FIFA World Cup. My favorite sports to bet on are the NFL, Nascar, College Hoops, and College Football.

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