49ers vs Cardinals Predictions & Best Bets

Last Updated: Dec 15, 2023

The San Francisco 49ers crushed the Arizona Cardinals in Week 4, and there should be a similar result on Sunday.

The 49ers are the only double-digit favorite among the NFL Week 15 odds, while the Cardinals are trending toward a top-five pick in next year’s NFL Draft.

It isn’t likely to be a competitive game, but there are a handful of intriguing wagering options to add excitement.

49ers vs Cardinals Odds

NFL odds used for this San Francisco vs Arizona preview were found at Caesars Sportsbook and are current as of December 13 at 9:30 p.m. ET.

  • Moneyline: 49ers (-900) • Cardinals (+600)
  • Spread: 49ers -12.5 (-110) • Cardinals +12.5 (-110)
  • Total Points: Over 48 (-110) • Under 48 (-110)
  • Implied Score: 49ers 30.25, Cardinals 17.75

49ers vs Cardinals Predictions

Score Pick: 49ers 38, Cardinals 17

The projected score is close to a copy and paste from San Francisco’s 35-16 victory against Arizona in Week 4. Yet it’s not as simple as expecting nearly the same result.

The Cardinals were starting Joshua Dobbs earlier in the season and will start Kyler Murray in the rematch. Nevertheless, Arizona’s lousy defense is unlikely to slow San Francisco’s star-studded offense.

Brock Purdy, Christian McCaffrey, Deebo Samuel, Brandon Aiyuk, George Kittle, and Trent Williams are healthy, which is terrible news for the Cardinals. According to FTN Fantasy, San Francisco’s offense is first in defense-adjusted value over average (DVOA).

Conversely, Arizona’s defense is 31st in defense DVOA. It’s unfair to look at Arizona’s offense DVOA since Murray has only started four games. Still, Murray won’t fix the other side of the ball.

There are a handful of critical players on San Francisco’s defense on the injury report, such as Javon Hargrave (hamstring), Charvarius Ward (groin), Dre Greenlaw (hip, ankle), and Arik Armstead (foot, knee).

Regardless, it still has game-wreckers like Nick Bosa, Chase Young, and Fred Warner to carry the defense if some of those injured teammates can’t suit up.

The 49ers are much better than the Cardinals on both sides of the ball. Therefore, the visitors should smash their hosts.

49ers vs Cardinals Best Bets & Props

49ers Over 30.5 (-110)

Caesars Sportsbook • WAGER: 1 unit

The 49ers have been healthy and destroying their opponents since their bye in Week 9. In five subsequent contests, they’ve averaged 32.4 points per game, with a median of 31.

Conversely, the Cardinals can’t stop anyone. They’ve allowed 25.5 points per game and a median of 26 this season. Thus, the 49ers totaling Over 30.5 points is my NFL bet of the day.

Christian McCaffrey Over 87.5 Rushing Yards (-119)

Caesars Sportsbook • WAGER: 0.5 units

McCaffrey is cutting through defenses like a hot knife through butter. He’s averaged 90.5 rushing yards per game, with a median of 93.

Moreover, CMC has averaged 103.5 rushing yards per game, with a median of 100.5, in San Francisco’s 10 wins. The stud running back has fallen short of 87.5 rushing yards only three times in victories this season.

The matchup is also mouthwatering for him. The Cardinals have coughed up 149.8 rushing yards per game at 5.2 yards per carry to running backs since Week 10.

Finally, six running backs have exceeded 87.5 rushing yards against the Cardinals, with Kyren Williams accomplishing the feat twice.

49ers -12.5 (-110)

Caesars Sportsbook • WAGER: 0.25 units

According to Covers, the 49ers are 7-6 against the spread (ATS) this season. They were just 2-2 ATS when favored by double-digit points. However, one of those victories was against the Cardinals in Week 4.

San Francisco also isn’t a stranger to boat racing opponents. It has beaten eight opponents by more than 12.5 points. Furthermore, it has beaten four of five opponents by more than 12.5 points since its bye.

49ers vs Cardinals Same-Game Parlay

49ers vs Cardinals SGP (+165)

Caesars Sportsbook • WAGER: 0.75 units

  • 49ers -9.5 (-166)
  • Christian McCaffrey 16+ Rush Attempts (-520)
  • Christian McCaffrey Over 87.5 Rushing Yards (-119)

The 49ers should cover the 12.5-point spread. Still, taking the chalkier alternate line at 9.5 points is appealing to enhance the odds of hitting this same-game parlay (SGP).

CMC has exceeded 87.5 rushing yards in seven of 10 wins this year. In addition, he’s had at least 16 rush attempts in all 10 wins.

So, the 49ers covering a 9.5-point spread correlates with CMC’s rushing yardage and rush attempts props. And, obviously, it’s always ideal to correlate legs in an SGP.


Josh Shepardson

Josh is a fantasy gamer of roughly 20 years and a fantasy pundit for more than 10 years. He's experienced in numerous season-long baseball and football league types and a daily fantasy sports grinder, too. Additionally, Josh is a recreational gambler who has a soft spot for futures and prop bets. He studied and completed his Bachelor's degree in Sport Management at the State University of New York at Cortland, and he remains in Central New York, residing in Auburn.

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