👇 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.
| ⭐ Favorite | San Francisco 49ers |
| 🔢 Point Spread | Cardinals +3, 49ers -3 |
| 📊 Moneyline | Cardinals +136, 49ers -162 |
| 📈 Game Total | Over/under 45.5 points (-110, -110) |
| ✅ Last Verified | October 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:
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.
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
| Date | Matchup | Winner |
|---|---|---|
| Oct. 31, 2019 | SF @ AZ | 49ers 28-25 |
| Nov. 25, 2007 | SF @ AZ | 49ers 37-31 |
| Dec. 12, 2004 | SF @ AZ | 49ers 31-28 |
| Oct. 10, 2004 | AZ @ SF | 49ers 31-28 |
| Nov. 6, 1988 | SF @ PHX | Cardinals 24-23 |
FAQs
Sportsbooks have the San Francisco 49ers as 3-point favorites over the Arizona Cardinals for the Week 3 matchup. Keep an eye on the lines, as they could move before kickoff depending on injuries or other news throughout the week.
The over/under for the Cardinals vs 49ers Week 3 matchup is set at 45.5 points. We don’t expect this number to move much more before kickoff. Last year, the two teams combined for 47 points in their first meeting and 71 points in their season finale.
You can place bets on the Cardinals vs 49ers at any legal sportsbook in Arizona. You just need to be 21 or older, located within state lines, and have an account with your chosen betting app. Don’t forget to take advantage of promos to maximize your potential winnings.
The Cardinals and 49ers meet in Week 3 on Sunday, September 21, at Levi’s Stadium in California, with kickoff set for 1:25 p.m. MST. They’ll face off again in Week 11 on November 16 at State Farm Stadium in Arizona.
The Cardinals vs 49ers Week 3 game will air live on FOX in local markets. Out-of-market viewers can watch via NFL Sunday Ticket on YouTube TV. Check 506sports.com to see if the game is available in your area.
Author
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.
