When the Arizona Cardinals play the San Francisco 49ers at 4:25 p.m. ET on Sunday, Sept. 21, our projection system predicts the Cardinals will come out on top. Our model also projects the spead, point total, and final score, which you can see below.
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49ers vs. Cardinals Game Info and TV Channel
- When: Sunday, September 21, 2025 at 4:25 p.m. ET
- Where: Levi's Stadium in Santa Clara, California
- TV: FOX
- Live Stream: Watch this game on Fubo (Regional restrictions may apply)
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49ers vs. Cardinals Odds and Betting Info
- Spread favorite: 49ers (-2.5)
- Moneyline: 49ers (-133), Cardinals (+113)
- Total: 45.5 points
49ers vs. Cardinals Prediction
- Pick ATS: Cardinals (+2.5)
- Pick OU: Over (45.5)
Prediction:
Cardinals 25 - 49ers 22
Prediction derived from a team strength comparison algorithm. Multiple factors such as strength of wins and scoring margin are used to make this projection.
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49ers vs. Cardinals Betting Insights
- The 49ers have compiled a perfect 2-0-0 record against the spread this season.
- The Cardinals have covered once in two games ATS this year.
- San Francisco has been favored by 2.5 points or more once this season, and covered the spread.
- 49ers games have gone over the point total once this season.
- So far this season, one Cardinals game has hit the over.
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