Arizona Cardinals vs. San Francisco 49ers early prediction: Expert picks for NFL Week 3, 2025

The Arizona Cardinals and San Francisco 49ers will meet in Week 3 of the NFL season at Levi's Stadium on Sunday, September 21, 2025, starting at 4:25PM ET.

Initial simulations from Dimers' trusted NFL model favor the 49ers as the most likely winner of this matchup.

For updates all week long, including best bets, player prop projections and touchdown probabilities, check out our interactive Cardinals vs. 49ers predictions page.

Arizona vs. San Francisco early predictions

Leveraging trusted machine learning and analysis, we have simulated the Cardinals vs. Niners game 10,000 times as part of our NFL predictions coverage. Here are the latest insights:

• Straight up win probabilities: Cardinals 39%, 49ers 61%
• Predicted final score: Cardinals 21-25 49ers
• Spread: Cardinals (+3.5) 50%, 49ers (-3.5) 50%
• Total points (47.5): Over 50%, Under 50%

As of September 14, 2025, these Cardinals-49ers figures and predictions reflect the latest data and insights available.

Cardinals vs. Niners Week 3 details

The NFL Week 3 action between the 49ers and Cardinals at Levi's Stadium is scheduled for September 21, 2025.

• Who: Arizona Cardinals vs. San Francisco 49ers
• Date: Sunday, September 21, 2025
• Time: 4:25PM ET/1:25PM PT
• Venue: Levi's Stadium

Cardinals vs. Niners opening odds

We've researched the best betting odds across America for this Week 3 game, which are listed here:

• Spread: Cardinals +3.5 (-105), 49ers -3.5 (-110)
• Moneyline: Cardinals +164, 49ers -180
• Total: Over/Under 47.5 (-110/-105)

Odds may continue to move—track live changes via our NFL odds page.

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Conclusion

We predict the 49ers, with a 61% win probability, will likely beat the Cardinals in Week 3 of the NFL season. Dimers.com will provide full game coverage closer to kickoff, so stay tuned for updates.

Enhanced by AI and automation, this article delivers quick, accurate insights on the Cardinals vs. 49ers matchup, with human oversight maintaining high editorial quality. Our predictions are sourced from the latest data to help you make informed decisions. For additional resources and advice on responsible gambling, please call 1-800-GAMBLER.

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