One Area the 49ers Have a Clear Advantage Over the Cardinals

The Cardinals will struggle against the 49ers in this one area when they square off in Week 3.

Sep 14, 2025; New Orleans, Louisiana, USA; New Orleans Saints running back Alvin Kamara (41) runs against San Francisco 49ers defensive tackle Alfred Collins (95) during the first half at Caesars Superdome. Mandatory Credit: Stephen Lew-Imagn Images | Stephen Lew-Imagn Images

A chance at opening the 2025 season with a 3-0 record is on the horizon for the San Francisco 49ers.

They'll have the opportunity to do that in front of their fans in their home opener in Week 3 against the Arizona Cardinals. Defeating the Cardinals won't be easy.

Despite not being a playoff-caliber team since 2021, the 49ers have their fits with the Cardinals. Part of that is the struggle with containing Kyler Murray as a rusher.

However, that is the only rushing element the 49ers will find challenging, as there is one area they have a clear advantage over the Cardinals.

One area the 49ers have an advantage over the Cardinals

Sep 14, 2025; New Orleans, Louisiana, USA; San Francisco 49ers linebacker Fred Warner (54) tackles New Orleans Saints running back Kendre Miller (5) during the second half at Caesars Superdome. Mandatory Credit: Stephen Lew-Imagn Images | Stephen Lew-Imagn Images

That advantage is the 49ers' run defense against the Cardinals' rushing offense. You couldn't say that last year, with the 49ers being subpar defending the run.

But things have changed in 2025. The Cardinals are currently ranked 30th in team rushing success rate (34.7 percent) through two weeks, per NFL Next Gen Stats (h/t Arizona Sports' Tyler Drake).

Meanwhile, the 49ers are ranked as the second-best in team run stuff rate (25 percent) and ninth-best in rush yards per play allowed (3.7).

Running backs James Connor and Trey Benson will find it difficult to seee big gains against the 49ers. Even without the stats to back it up, the 49ers have been visually solid defending the run.

They held up well against two amazing runners in Alvin Kamara, Zach Charbonnet, and Kenneth Walker in the last two weeks, especially against Walker.

Sep 7, 2025; Seattle, Washington, USA; Seattle Seahawks running back Zach Charbonnet (26) runs the ball during the second half against San Francisco 49ers at Lumen Field. Mandatory Credit: Steven Bisig-Imagn Images | Steven Bisig-Imagn Images

Look at how monstrous a game Walker had against the Pittsburgh Steelers in Week 2. He rushed for 105 yards and scored a touchdown on 13 carries.

He only managed to rush for 20 yards on 10 carries versus the 49ers. Clearly, the 49ers have improved as a run defense under Robert Saleh, and with the added rookies like Mykel Williams.

That should continue against Arizona this Sunday, especially since their rush success rate is the third-worst in the league.

Bottling up the ground game of Arizona will force them to drop back and pass more with Murray. All the 49ers have to do is key in on Marvin Harrison Jr. and Trey McBride in the pass game.

The real threat on the ground will be Murray's legs. Whether it's a designed run or a scramble play, that is where the 49ers have struggled defending against the Cardinals.

Last year, when the 49ers hosted the Cardinals, Murray ripped off a 50-yard touchdown run on their opening drive. I don't foresee that happening under a Saleh-led defense.

Everything will become easier for the 49ers against Arizona if their clear advantage sustains.

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