Cardinals vs 49ers Prediction, Picks & Odds | 21 Sep 2025

NFL Betting Preview: Cardinals vs Niners

The Arizona Cardinals face the San Francisco 49ers in this NFL Week 3 matchup at Levi's Stadium, with kickoff scheduled for 16:25 on Sunday, September 21. Our betting preview features expert predictions, picks, updated betting odds, head-to-head stats and the latest team news, including injuries.

The Cardinals should be able to outscore the Niners and our prediction is to side with them on the Moneyline. There is a tempting +110 should you wish to follow suit.

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Arizona Cardinals claimed a home victory in their previous game. A 27-22 triumph against Carolina Panthers at State Farm Stadium made it back-to-back wins. The Cardinals put up 293 yards, including 211 passing and 82 rushing yards. The offense managed 16 first downs and reached the end zone 3 times, 1 via the pass and 1 on the ground.

San Francisco 49ers have triumphed in back-to-back games. The latest of these was on the road where New Orleans Saints were beaten 26-21 at Caesars Superdome. The 49ers totaled 344 yards, with 267 through the air and 77 on the ground. They scored 3 touchdowns and picked up 23 first downs.

Head-to-Head Statistics

The Cardinals have beaten the Niners in the last two matchups. A 24-23 victory at Levi's Stadium was followed by a 47-24 win at State Farm Stadium. Both teams have won five games when it comes to the previous 10 H2H meetings.

Quarterbacks

Kyler Murray

215.5 Passing Yards

Over -112

Under -112

Mac Jones

222.5 Passing Yards

Over -112

Under -112

Cardinals vs 49ers Prediction & Picks

The Cardinals vs 49ers betting tips feature sharp analysis across major markets, including a key match prediction, player prop bets, correct score guidance and a ready-made bet builder.

Game Prediction

We are eager to back the Cardinals to win this NFL matchup and that leads us to the Moneyline for our pick. It’s difficult to turn down the +110 that they claim the win.

The NFL handicappers at Sportsgambler.com start by analyzing recent form and staying on top of injury news before making any predictions. From there, we interpret the story the stats are telling to help shape our picks.

Key Cardinals vs 49ers stats:

• Cardinals have won 3 consecutive games.
• 49ers have lost 7 of their last 10 games.
• 49ers have lost 12 of their last 20 games.
• 49ers have lost their last 2 games at home.
• 49ers have lost their last 2 games against Cardinals.

Cardinals Moneyline Probability

If you go by the top betting sites, there’s a 47.6% likelihood of our pick landing a return. In the opinion of our analysts, there’s actually a probability of success between 50-55%. It’s why we think it’s worth placing this bet.

If you’re looking to squeeze more juice from the odds, consider the Cardinals on the spread. Those expecting this franchise to exceed expectations can bet them to cover the line.

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Our Game Prediction

Cardinals Moneyline @ +110 Bet Now

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Disclosure: This preview contains affiliate links; we may earn a commission at no extra cost to you. T&Cs apply. We only recommend licensed and regulated operators. See our Editorial Policy. Pick odds and lines reflect the price available at the time of publication (22:26, 19 September 2025). Live market odds are updated regularly and may differ. 18+ (or legal age) | Gamble Responsibly.

Player Prop Picks

Top Pick: Kyler Murray Over 215.5 Passing Yards -114

Kyler Murray (Cardinals) can be backed at -114 to exceed 215.5 passing yards. The line for him on the Overs is highly appealing, with QB Passing Yards bettors able to get plenty of juice.

Latest Kyler Murray Player Prop Odds

Touchdown

Anytime

+290

First

+1400

Passing Yards

Over 215.5

-112

Under 215.5

-112

Rushing Yards

Over 28.5

-112

Under 28.5

-112

---

Trey McBride Anytime TD +200

The odds for Trey McBride (Cardinals) to hit paydirt are +200. We believe this is the best of the player props, with attractive odds available when it comes to betting him to score a touchdown at any time.

Latest Trey McBride Player Prop Odds

Touchdown

Anytime

+200

First

+1100

Receiving Yards

Over 62.5

-112

Under 62.5

-112

Pick odds and lines correct at publication. Live market odds are updated regularly and may differ. T&Cs apply. 18+ (or legal age) | Gamble Responsibly.

Correct Score Prediction

Cardinals 31 - 23 49ers

For those looking to get more bang for their buck, consider a correct score bet on the Cardinals. Backing them to win 31-23 means you can land a potential monster return.

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Cardinals vs 49ers Odds

The odds and lines below are updated regularly and may differ from the prices shown in our picks, which are captured at the time of publication.

When you consider the latest Moneyline odds, you can find San Francisco 49ers at -122 whereas Arizona Cardinals are +104. This means the leading sportsbooks give the visiting team a 49% chance of success.

The spread currently stands at 1.5 and the total points line is 44.5. Having a wager on the Totals is one of the most popular NFL bets. There’s the chance to back Under 44.5 at -110.

The best NFL sportsbooks offer a wide range of team props and game lines for every matchup. Make sure you look through all the available options before deciding which bet to place.

Moneyline

Cardinals

+104

49ers

-122

Point Spread

Cardinals +1.5

-110

49ers -1.5

-110

Total Points

Under 44.5

-110

Over 44.5

-110

The First Touchdown Scorer favorite is Christian McCaffrey at +380. Similar odds can be found if you’re interested in this player to register the final TD.

Touchdown

Christian McCaffrey (49ers)

First TD

+380

Anytime TD

-179

James Conner (Cardinals)

First TD

+600

Anytime TD

+105

Ricky Pearsall (49ers)

First TD

+1000

Anytime TD

+180

Marvin Harrison Jr. (Cardinals)

First TD

+1100

Anytime TD

+180

Trey McBride (Cardinals)

First TD

+1100

Anytime TD

+200

Trey Benson (Cardinals)

First TD

+1200

Anytime TD

+250

Jauan Jennings (49ers)

First TD

+1200

Anytime TD

+210

Kyler Murray (Cardinals)

First TD

+1400

Anytime TD

+290

Kendrick Bourne (49ers)

First TD

+1700

Anytime TD

+340

Brian Robinson Jr. (49ers)

First TD

+2000

Anytime TD

+450

Michael Wilson (Cardinals)

First TD

+2200

Anytime TD

+420

Kyle Juszczyk (49ers)

First TD

+2500

Anytime TD

+550

Mac Jones (49ers)

First TD

+2700

Anytime TD

+600

Jake Tonges (49ers)

First TD

+2700

Anytime TD

+500

Russell Gage (49ers)

First TD

+3500

Anytime TD

+750

Marquez Valdes-Scantling (49ers)

First TD

+3500

Anytime TD

+800

Elijah Higgins (Cardinals)

First TD

+4500

Anytime TD

+1000

Zay Jones (Cardinals)

First TD

+5000

Anytime TD

+1300

Luke Farrell (49ers)

First TD

+5000

Anytime TD

+1200

Greg Dortch (Cardinals)

First TD

+6000

Anytime TD

+1300

Emari Demercado (Cardinals)

First TD

+7000

Anytime TD

+1300

Travis Vokolek (Cardinals)

First TD

+8000

Anytime TD

+1900

Skyy Moore (49ers)

First TD

+8000

Anytime TD

+1900

Xavier Weaver (Cardinals)

First TD

+8000

Anytime TD

+1500

Bam Knight (Cardinals)

First TD

+8000

Anytime TD

+1100

Tip Reiman (Cardinals)

First TD

+10000

Anytime TD

+2500

Isaac Guerendo (49ers)

First TD

+10000

Anytime TD

+2000

Simi Fehoko (Cardinals)

First TD

+10000

Anytime TD

+2200

Brayden Willis (49ers)

First TD

+10000

Anytime TD

+2700

James Jordan (49ers)

First TD

+10000

Anytime TD

+1500

Receiving Yards

Ricky Pearsall (49ers)

Over 68.5

-112

Under 68.5

-112

Trey McBride (Cardinals)

Over 62.5

-112

Under 62.5

-112

Marvin Harrison Jr. (Cardinals)

Over 49.5

-112

Under 49.5

-112

Christian McCaffrey (49ers)

Over 40.5

-112

Under 40.5

-112

Kendrick Bourne (49ers)

Over 31.5

-112

Under 31.5

-112

Michael Wilson (Cardinals)

Over 25.5

-112

Under 25.5

-112

Jake Tonges (49ers)

Over 21.5

-112

Under 21.5

-112

James Conner (Cardinals)

Over 13.5

-112

Under 13.5

-112

Rushing Yards

Christian McCaffrey (49ers)

Over 68.5

-112

Under 68.5

-112

James Conner (Cardinals)

Over 54.5

-112

Under 54.5

-112

Kyler Murray (Cardinals)

Over 28.5

-112

Under 28.5

-112

Trey Benson (Cardinals)

Over 25.5

-112

Under 25.5

-112

Brian Robinson Jr. (49ers)

Over 20.5

-112

Under 20.5

-112

Mac Jones (49ers)

Over 6.5

-112

Under 6.5

-112

Passing Yards

Mac Jones (49ers)

Over 222.5

-112

Under 222.5

-112

Kyler Murray (Cardinals)

Over 215.5

-112

Under 215.5

-112

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Niners Hold Five Wins in Previous Ten at Home

The Niners have a 5-5 record in their last 10 home games, scoring 26.20 points per contest and conceding 22.40.

The Cardinals own a 4-6 mark in their past 10 road games, averaging 21.50 points scored and 25.00 points allowed.

The last time the teams met at Levi's Stadium, the Cardinals defeated the Niners 24-23. The last 6 head-to-head matchups at Levi's Stadium have been split, with each team winning three times.

Last 10 Games		W-L	P	PF	PA	O44.5	U44.5
49ers Home Stats		5-5	48.60	26.20	22.40	7	3
Cardinals Away Stats		4-6	46.50	21.50	25.00	7	3

• W-L = Wins-Losses
• P = Avg. Points
• PF = Avg. Points For
• PA = Avg. Points Against
• O44.5 = Games Over 44.5 Points
• U44.5 = Games Under 44.5 Points

Latest regular season and playoff games stats.

Arizona Cardinals Stats

San Francisco 49ers Stats

Moneyline

• 5 wins and 5 defeats in the last 10 games
• 4 wins and 6 defeats in the last 10 games on the road

Moneyline

• 3 wins and 7 defeats in the last 10 games
• 5 wins and 5 defeats in the last 10 home games

Point Spread

• +2.5 Betting Line: Have covered the spread in 6 of the last 10 games
• +2.5 Betting Line on the Road: Have covered the spread in 5 of the last 10 games on the road

Point Spread

• -2.5 Betting Line: Have covered the spread in 3 of the last 10 games
• -2.5 Betting Line at Home: Have covered the spread in 5 of the last 10 home games

Total Points

• Game Totals: An average of 44.00 pts in the previous 10 games
• Game Totals on the Road: An average of 46.50 pts in the previous 10 games on the road
• Over 44.5: Covered in 6 of the previous 10 games
• Over 44.5 on the Road: Covered in 7 of the previous 10 games on the road
• Team Totals: Have scored an average of 24.00 pts and allowed 20.00 pts in the last 10 games
• Team Totals on the Road: Have scored an average of 21.50 pts and allowed 25.00 pts in the last 10 games on the road

Total Points

• Game Totals: An average of 46.70 pts in the previous 10 games
• Game Totals at Home: An average of 48.60 pts in the previous 10 home games
• Over 44.5: Covered in 7 of the previous 10 games
• Over 44.5 at Home: Covered in 7 of the previous 10 home games
• Team Totals: Have scored an average of 19.90 pts and allowed 26.80 pts in the last 10 games
• Team Totals at Home: Have scored an average of 26.20 pts and allowed 22.40 pts in the last 10 home games

Game Stats

Last 10 Games

• Total Yards: Gained 359.80 Yds. Allowed 318.50 Yds
• Rushing Yards: Gained 131.50 Yds. Allowed 105.30 Yds
• Passing Yards: Gained 228.30 Yds. Allowed 213.20 Yds
• Total Touchdowns: Scored 2.50 TD. Allowed 2.20 TD
• Rushing Touchdowns: Scored 1.00 TD. Allowed 0.90 TD
• Passing Touchdowns: Scored 1.30 TD. Allowed 1.30 TD
• Total 1st Downs: Picked up 21.70. Allowed 19.30
• Total Turnovers: Committed 1.00. Committed by opponents 0.90
• Total Penalties: Committed 7.00. Committed by opponents 7.30
• Penalty Yards: Lost 58.80 Yds. Gained 60.60 Yds

Game Stats

Last 10 Games

• Total Yards: Gained 341.30 Yds. Allowed 319.20 Yds
• Rushing Yards: Gained 101.20 Yds. Allowed 136.90 Yds
• Passing Yards: Gained 240.10 Yds. Allowed 182.30 Yds
• Total Touchdowns: Scored 2.40 TD. Allowed 3.10 TD
• Rushing Touchdowns: Scored 0.80 TD. Allowed 1.40 TD
• Passing Touchdowns: Scored 1.60 TD. Allowed 1.70 TD
• Total 1st Downs: Picked up 20.20. Allowed 19.50
• Total Turnovers: Committed 1.90. Committed by opponents 0.50
• Total Penalties: Committed 7.30. Committed by opponents 4.40
• Penalty Yards: Lost 50.30 Yds. Gained 34.70 Yds

Last 10 Games on the Road

• Total Yards: Gained 352.40 Yds. Allowed 329.50 Yds
• Rushing Yards: Gained 133.60 Yds. Allowed 119.80 Yds
• Passing Yards: Gained 218.80 Yds. Allowed 209.70 Yds
• Total Touchdowns: Scored 2.00 TD. Allowed 2.80 TD
• Rushing Touchdowns: Scored 0.60 TD. Allowed 0.90 TD
• Passing Touchdowns: Scored 1.30 TD. Allowed 1.70 TD
• Total 1st Downs: Picked up 21.20. Allowed 20.00
• Total Turnovers: Committed 1.30. Committed by opponents 0.80
• Total Penalties: Committed 7.00. Committed by opponents 6.10
• Penalty Yards: Lost 53.50 Yds. Gained 49.60 Yds

Last 10 Home Games

• Total Yards: Gained 380.30 Yds. Allowed 309.50 Yds
• Rushing Yards: Gained 136.00 Yds. Allowed 118.80 Yds
• Passing Yards: Gained 244.30 Yds. Allowed 190.70 Yds
• Total Touchdowns: Scored 2.80 TD. Allowed 2.60 TD
• Rushing Touchdowns: Scored 1.60 TD. Allowed 1.40 TD
• Passing Touchdowns: Scored 1.00 TD. Allowed 1.20 TD
• Total 1st Downs: Picked up 20.90. Allowed 18.30
• Total Turnovers: Committed 1.50. Committed by opponents 1.30
• Total Penalties: Committed 5.60. Committed by opponents 3.50
• Penalty Yards: Lost 37.70 Yds. Gained 27.50 Yds

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