Week 3 Staff Predictions: Arizona Cardinals at San Francisco 49ers

This is shaping up to be a close NFC West battle.

Aug 9, 2025; Glendale, Arizona, USA; Arizona Cardinals wide receiver Marvin Harrison Jr. (18) against the Kansas City Chiefs during a preseason NFL game at State Farm Stadium. Mandatory Credit: Mark J. Rebilas-Imagn Images | Mark J. Rebilas-Imagn Images

The Arizona Cardinals and San Francisco 49ers will meet at Levi's Stadium later today with both ball clubs hoping to reach a 3-0 record.

Staff predictions from us at Cardinals On SI:

Donnie Druin - SF 21, AZ 17

This has the opportunity to either be a shootout or a snooze-fest, and I’m leaning a bit more towards the latter with injuries galore on both sides. I think whoever wins this matchup will only do so by one possession goal, but give me the 49ers thanks to their structural stability at the moment - I want to see how the Cardinals react to having a handful of key pieces down.

Sep 14, 2025; New Orleans, Louisiana, USA; San Francisco 49ers quarterback Mac Jones (10) drops back to pass against the New Orleans Saints during the first half at Caesars Superdome. Mandatory Credit: Stephen Lew-Imagn Images | Stephen Lew-Imagn Images

READ: Answering Arizona Cardinals Biggest Week 4 Questions

Richie Bradshaw - AZ 20, SF 14

I’m putting a lot of stock in this game being atrocious to watch. Both teams are dealing with major injuries and haven’t found their grooves in playing to their (perceived) respective strengths. The difference in this game will come down to who can make the clutch moments… and a lot of that will be placed on the legs of each team‘s kicker. That’s the biggest difference between these teams, and that’s why the Cardinals will emerge victorious, as Chad Ryland will come through clutch while the 49ers continue their kicking struggles. 

READ: 49ers Ready to Get Tricky vs Cardinals

Kyler Burd - AZ 17, SF 13

Both of these teams are dealing with injuries at key positions so I won’t be surprised if this is a slow-paced game. I expect the Cardinals to try and key in on using Marvin Harrison, Jr. a bit more but the game will still flow through Trey McBride which could be enough to get in done. With a few lucky bounces their way the Cardinals can win this game but it will take a full-team effort. 

Arizona Cardinals quarterback Kyler Murray (1) throws the ball against the Carolina Panthers at State Farm Stadium on Sept 14, 2025. | Joe Rondone/The Republic / USA TODAY NETWORK via Imagn Images

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Sam Dehring - AZ 20, SF 13

I think the Cardinals come away with a win in a close one. Both teams are dealing with injuries. I think the key to this game is going to be getting Marvin Harrison Jr. more involved in the passing game. The run game last week did struggle. They’re going to be too really get the run game going.

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