49ers vs. Cardinals: The Standard’s 5 fast predictions

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Can the 49ers survive without Brock Purdy on the field?

If Sunday’s matchup with the New Orleans Saints was any indication, backup Mac Jones is more than capable as a fill-in. Jones lacks Purdy’s mobility and the knack for extending plays when the pocket collapses, but the former Patriots and Jaguars quarterback has already proved he has the arm talent and processing ability to lead the 49ers’ offense. 

Now comes a much more challenging test.

As Purdy continues to recover from a toe injury, Jones is likely to start the home-opener Sunday at Levi’s Stadium against the 2-0 Arizona Cardinals. This opponent dismantled Kyle Shanahan’s team in last year’s season finale, a 47-24 blowout in Glendale, but that defeat came at the end of a nightmare season.

What’s in store for the 49ers’ second divisional matchup of 2025? The Standard’s Tim Kawakami and David Lombardi are back with their weekly predictions. 

Kawakami: Kyler Murray. Well, this might be tipping my game prediction more than a bit, but so it goes. Murray’s always been a problem for the 49ers’ defense (just check the tape from last year or any year), and I think the younger players might need some time to get up to his speed. Maybe by the Nov. 16 matchup in Arizona, but I’m guessing not this one.

Lombardi: Ricky Pearsall. The Cardinals were roaring along defensively … until the stretch run of their Week 2 win, when the Carolina Panthers almost erased a big deficit. Arizona’s mounting injuries in the secondary certainly played a part. The Cardinals, who were already down cornerback Sean Murphy-Bunting, placed fellow DB Garrett Williams on injured reserve in recent days. Rookie starter Will Johnson has yet to practice this week.

The 49ers should have opportunities to attack downfield regardless of who’s playing QB.

Kawakami: Mykel Williams. A measure of DeForest Buckner’s greatness during his 49ers tenure is that he was the only defensive lineman who had the reflexes and determination to reliably catch the speediest QBs on broken plays. Williams might step into that void, starting Sunday. I’ll even predict that he’ll get his first NFL sack.

Lombardi: Upton Stout. Murray is short and very quick. On the other side, those same descriptors apply to Stout, who projects to be a valuable weapon in the containment of mobile quarterbacks. Last week, 49ers defensive coordinator Robert Saleh used Stout on a series of aggressive blitzes. Even if Saleh plays this one more conservatively, Stout’s nickelback role is critical in run defense — and that’s particularly big with Murray and Cardinals running back James Conner threatening the 49ers on read option plays.

Kawakami: Kendrick Bourne. I suspect that Pearsall’s big early production (20.5 yards per catch through the first two games) is now on every opponent’s radar. I think defenses also know that Jones — if Purdy can’t make it back — likes to throw to his tight ends. Which could open space for a trusty veteran WR on key plays.

Lombardi: Christian McCaffrey. He’s dominated both of the 49ers’ first two opponents as a receiver. It’s at the point where opposing defenses will have to start shading their attention toward pass defense — and that’s precisely what can open running lanes for McCaffrey. Even if the 49ers are missing numerous key weapons, McCaffrey’s multi-threat adaptability can erase a whole lot of deficiencies.

Kawakami: McCaffrey total yards. Intentional or not, there’s an early pattern developing: McCaffrey had 31 touches and produced 142 yards against divisional foe Seattle, then was down to 19 touches for 107 yards against non-NFC West opponent New Orleans. If Shanahan’s intent is to heighten McCaffrey’s impact specifically for division games — like Sunday’s — it’d be logical. The 49ers might need 30 touches and 150 yards from McCaffrey in this one.

Lombardi: 49ers’ yards per carry. I picked this stat last week and will continue selecting it until the 49ers’ run game clicks. They managed just 3.0 yards per carry in New Orleans, thanks to a confluence of factors — primarily the Saints’ insistence on stopping the run.

“The Saints were playing a lot of people close to the line of scrimmage,” 49ers GM John Lynch said on KNBR, “so we threw it 39 times.”

Mark my words: An adjustment is coming. The 49ers have enjoyed enough passing success to predict that there will be more openings for the run against Arizona.

Kawakami: Arizona 20, 49ers 13. Could the 49ers steal another one without Purdy? Sure. Arizona is 2-0 but was out-gained in both games. I just don’t see Arizona’s defense giving up much on the ground, which could put a little more pressure on the 49ers’ passing game than it is ready to handle. And I’m writing Murray down for at least two TDs.

Lombardi: 49ers 21, Cardinals 20. This is the most talented Arizona team that Shanahan has faced in his nine seasons. The D-line additions of veterans Josh Sweat, Dalvin Tomlinson, and Calais Campbell promise to give this game a heavyweight-fight feel. But the 49ers have clearly gotten faster, and that’ll come in handy against Murray. Then, Arizona’s injury troubles in the secondary will give Shanahan’s shorthanded offense enough chances to open 3-0.