The San Francisco 49ers are taking on the Arizona Cardinals in their home opener of the 2025 season in a divisional battle between two undefeated teams.

San Francisco kicked off the year with a 17-13 road victory over the Seattle Seahawks before their 26-21 win over the New Orleans Saints in Louisiana last weekend.

Both wins have come with some strong defensive play to close things out, as Robert Saleh’s unit has performed well, despite relying on younger pieces to step up and play.

San Francisco will likely be starting Mac Jones for the second straight week. Brock Purdy was a limited participant in practice this week as he recovers from his toe injury, but head coach Kyle Shanahan said it was highly unlikely he’d start on Sunday.

It’s unclear whether the 49ers will have Purdy as the No. 2 quarterback or the No. 3 option on Sunday, though, as San Francisco also has practice squad signal-caller Adrian Martinez, who was called up to play last week.

They’re taking on an Arizona Cardinals team that has beaten the Saints and the Carolina Panthers to start the year 2-0. Arizona has been a good defensive team so far, and will present a rushing threat at quarterback with Kyler Murray at the helm.

Here are three keys to a 49ers win over the Cardinals on Sunday.

Set edges well

Kyler Murray has had some of the best rushing games of his career against the 49ers. Four of his top 11 games in rushing yards have come against San Francisco, which has struggled at times to defend mobile quarterbacks.

Over the first two games of the season, Murray hasn’t run the ball much, going for 70 yards on 14 attempts. But, the Cardinals have struggled to run the ball as a whole. While Trey Benson has averaged 7.5 yards per attempt on the ground, lead back James Conner has gone for a measly 3.2 yards per carry to start the year.

Murray could be involved more on the ground, so the 49ers will need to contain the pocket well, which starts with edge rushers Mykel Williams and Nick Bosa.

Williams has started the season well, and Week 3 could be his biggest challenge yet. If San Francisco contains the run from the edges, they’ll be in a good position against Murray and the Cardinals offense.

Let Mac Cook

The Cardinals have one of the better defenses in the NFL so far. Yes, they’re ranked in the bottom half in yards allowed. But, that’s because teams have had to come back against them in both wins, being forced to pass at a high volume so far.

The Cardinals are sixth in rushing yards allowed per game (78), 10th in yards per attempt allowed (3.8), and ninth in passer rating allowed (81.4). They’ll be looking to stop the run, and the 49ers are banged up along the offensive line with left guard Connor Colby dealing with an injury.

San Francisco will absolutely have to run the ball and get success with Christian McCaffrey there. But, they executed well with schemed-open receivers, and head coach Kyle Shanahan trusted Mac Jones in the dropback game.

With Arizona down several cornerbacks, the 49ers need success through the air. They’re going to need another solid performance from Jones here.

Red zone execution

One area that the 49ers have struggled with to begin the season is execution in the red zone. San Francisco was middle of the pack last year with red zone execution, but was first in the NFL in 2023 with a stellar 68.5 percent touchdown rate.

Right now, they’re tied with the Cardinals at 16th in the NFL with a 57.1 percent touchdown rate. Defensively, they’ve allowed four touchdowns on six red zone opportunities, including three scores last week. Arizona is better, ranking 11th with a 50 percent touchdown rate allowed through two games.

San Francisco has really struggled to run the ball in the red zone. They’ll need to improve there. But, red zone execution could very well be a determining factor, given how close this divisional rivalry has been in the past.

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