Cardinals vs 49ers Week 3 Odds: San Franciso Favored at Home

Wes Roesch Profile Picture

Key Takeaways:

  • 🏆 Favorite: The 49ers are favorites against the Cardinals in Week 3.
  • 💪 Cardinals' Chances: Arizona has a 42.4% chance to beat the Niners.
  • 👀 Point Spread: The Cardinals sit at +3 vs the 49ers.
  • 📝 Over/Under: The over/under for Cardinals vs 49ers Week 3 is set at 45.5 points.
  • 💲 Moneyline: The Cardinals' moneyline is +136, while the 49ers' sit at -162.

The Arizona Cardinals face NFC West rival San Francisco twice every season, with the first matchup coming in Week 3 at Levi’s Stadium. San Francisco is a 3-point home favorite, but the Cardinals will look to extend their win streak after sweeping the 49ers 2-0 last season. Early-season injuries for San Francisco could give Arizona an edge on the road, as both teams enter the game 2-0.

Find the latest odds and lines for Cardinals vs 49ers from top Arizona sportsbooks.

👇 Cardinals vs. 49ers Odds: Quick Facts 👇

Below are the latest odds for the Week 3 Cardinals vs 49ers matchup. Expect movement before kickoff, as lines often vary across sportsbooks.

⭐ FavoriteSan Francisco 49ers
🔢 Point SpreadCardinals +3, 49ers -3
📊 MoneylineCardinals +136, 49ers -162
📈 Game TotalOver/under 45.5 points (-110, -110)
✅ Last VerifiedOctober 17, 2025

Odds via DraftKings Sportsbook.

Who Is Favored to Win?

The San Francisco 49ers are favored in Week 3, largely because of home-field advantage. Still, the Cardinals have a real chance to pull off the upset, especially with key 49ers injuries to quarterback Brock Purdy and tight end George Kittle. Final injury reports for both teams will provide more clarity as kickoff approaches.

What's the Point Spread?

The Week 3 point spread for Cardinals vs 49ers is currently San Francisco -3 and Arizona +3. With both teams undefeated, these odds could shift leading up to kickoff. For example, the Cardinals opened at +3.5, but their line improved after back-to-back wins.

What's the Moneyline?

The moneyline for Cardinals vs 49ers is set at AZ +136 and SF -162. Betting $100 on -162 would earn $61.73 plus your $100 back if the Niners win. Meanwhile, betting $100 on the Cards would earn you $136 plus your $100 back if Arizona wins straight up.

What's the Over/Under?

The total for the Cardinals vs 49ers Week 3 game is set at 45.5 points. Last season, the teams combined for 47 points in their first matchup and 71 in the season finale. While a high-scoring game seemed likely, if starting QB Brock Purdy is ruled out, we’re leaning toward the under.


Related Cardinals Betting Content:


Arizona Cardinals Chances to Win vs San Francisco 49ers

The Cardinals have a 48.2% chance to beat the 49ers in Week 3. Their chances are calculated using implied probability based on odds from DraftKings. Here is how it is calculated for each team using +136 odds for the Cardinals and -162 odds for the 49ers:

Cardinals chances: 136 ÷ (136 + 100) * 100 = 57.6%
49ers chances: 162 ÷ (162 + 100) * 100 = 61.8%

However, the above percentages add up to 119.4%. This is due to the vig, which is the house edge for the sportsbook which allows them to profit off the bet. To remove the vig, we simply divide each team's chance by 119.4.

Cardinals chances (after vig): 57.6 ÷ 119.4 = 48.2%
49ers chances (after vig): 61.8 ÷ 119.4 = 51.8%

Note that both of the final team chances above finally equal 100%. Hence, the 48.2% chance to win for the Cardinals.

How Arizona Wins vs San Francisco

The key to beating the 49ers could come down to the Cardinals’ offense. If Kyler Murray can fully leverage his dual-threat ability and the team utilizes its elite receiving talent, Arizona has a path to victory. Tight end Trey McBride will be crucial as a focal point in the passing game, especially in the middle of the field. If the defense can contain San Francisco’s run game and force turnovers, the Cardinals have a real shot at winning.


Other Cardinals Matchups This Season:


How San Francisco Wins vs Arizona

On the other side, the 49ers will need to contain Kyler Murray and stay disciplined against the Cardinals’ explosive offense. The game could come down to San Francisco’s defense making key stops while the offense relies on running back Christian McCaffrey to control the action.

How to Watch Cardinals vs. 49ers

The Cardinals vs 49ers Week 3 game airs on FOX in local markets at 1:25 p.m. MST on Sunday, September 21. Out-of-market viewers can watch via NFL Sunday Ticket, available exclusively on YouTube TV. Live TV streaming services, including YouTube TV, Hulu + Live TV, Fubo, and DIRECTV STREAM, also carry local FOX channels.

Exclusive Promos for Betting on the Game

There are many Arizona sports betting promos available to use for the Cardinals vs 49ers game. These promos can also be used on props, futures and other bets:

Must be 21+ to participate. Gambling Problem? Call 1-800-GAMBLER or visit FanDuel.com/RG (CO, IA, KY, MI, NJ, OH, PA, IL, TN, VA, VT), 1-800-NEXT-STEP or text NEXTSTEP to 53342 (AZ), 1-888-789-7777 or visit ccpg.org/chat (CT), 1-800-9-WITH-IT (IN), 1-800-522-4700 or visit ksgamblinghelp.com (KS), 1-877-770-STOP (LA), visit www.mdgamblinghelp.org (MD), 1-800-522-4700 (WY), or visit www.1800gambler.net (WV). GamblingHelpLineMA.org or call (800) 327-5050 for 24/7 support (MA). Call 1-877-8HOPE-NY or text HOPENY (467369) (NY).
Gambling problem? Call 1-800-GAMBLER (Available in the US) Call 877-8-HOPENY or text HOPENY (467369) (NY) Call 1-800-327-5050 (MA), 1-800-NEXT-STEP (AZ), 1-800-BETS-OFF (IA), 1-800-981-0023 (PR) 21+ only. Please Gamble Responsibly. See BetMGM.com for Terms. Subject to eligibility requirements. Bonus bets are non-withdrawable. In partnership with Kansas Crossing Casino and Hotel. This promotional offer is not available in DC, Mississippi, New York, Nevada, Ontario, or Puerto Rico.
Must be 21+ to participate. Gambling problem? Call 1-800-GAMBLER (CO, IL, IA, KY, KS, LA, MD, NC, NJ, OH, PA, TN, VA). Call 1-800-NEXT-STEP (AZ). Call 1-800-9-WITH-IT (IN). Deposit required. Paid in Bonus Bets. Bets wager excluded from returns. New Customer only. T&Cs, time limits and exclusions apply. Code is for marketing/tracking purposes.
GAMBLING PROBLEM? CALL 1-800-GAMBLER, (800) 327-5050 or visit gamblinghelplinema.org (MA). Call 877-8-HOPENY/text HOPENY (467369) (NY). Please Gamble Responsibly. 888-789-7777/visit ccpg.org (CT), or visit www.mdgamblinghelp.org (MD). 21+ and present in most states. (18+ DC/KY/NH/WY). Void in ONT/OR/NH. Eligibility restrictions apply. On behalf of Boot Hill Casino & Resort (KS). Pass-thru of per wager tax may apply in IL. 1 per new DraftKings customer. Must register new DraftKings account to receive reward Token. Must select Token BEFORE placing min. $5 bet to get 1 promo code to redeem 3-month NBA League Pass subscription, complimentary of DraftKings, and get max. $300 in Bonus Bets if your bet wins. Min. -500 odds req. Token and Bonus Bets are single-use and non-withdrawable. Bonus Bets expire in 7 days (168 hours) and stake removed from payout. Token expires 11/23/25. Terms: sportsbook.draftkings.com/promos. NBA League Pass: Subscription auto-renews monthly at then-current price (currently $16.99/mo); cancel anytime. Terms, restrictions, and eligibility requirements apply. Redeem League Pass by 12/19/25 at 11:59 PM ET. Addt’l terms: https://support.watch.nba.com/hc/en-us/articles/9165532876183-League-Pass-Terms-of-Use_. Offer ends 11/16/25 at 11:59 PM ET. Sponsored by DK.

Best Prop Picks for Cardinals vs 49ers

The widget below highlights popular Cardinals vs. 49ers prop bets, including anytime touchdown scorers. Always do your own research before placing any wagers.

San Francisco 49ers quarterback Brock Purdy shakes hands with Arizona Cardinals quarterback Kyler Murray

History of Cardinals vs. 49ers

The Cardinals and 49ers have played each other 67 times dating way back to 1951 when the Cardinals were called the Chicago Cardinals (and later St. Louis Cardinals, then later Phoenix Cardinals before becoming the Arizona Cardinals).

Record All-Time

The 49ers lead the all-time series 36-31 over the Cardinals, and were on a four-game winning streak before losing to the Cards early in the 2024 season.

Most Recent Matchup

The last meeting between the Cardinals and 49ers took place on January 5, 2025 at State Farm Stadium in Arizona. The Cards won 47-24, with QB Kyler Murray throwing for 242 yards and tight end Trey McBride hauling in seven receptions.

Top 5 Games

DateMatchupWinner
Oct. 31, 2019SF @ AZ49ers 28-25
Nov. 25, 2007SF @ AZ49ers 37-31
Dec. 12, 2004SF @ AZ49ers 31-28
Oct. 10, 2004AZ @ SF49ers 31-28
Nov. 6, 1988SF @ PHXCardinals 24-23

FAQs

Author

Wes Roesch

Wes is an editor and writer for BetArizona.com. Based out of the Kansas City area, Wes has covered sports professionally since 2015 with a strong emphasis on sports betting and the NFL, though he's also covered pro wrestling, UFC, college sports and more.

Cited by leading media organizations, such as: