The 49ers return home at 2-0 for their first divisional game of the season, while the Cardinals arrive at 1-1 after two markedly different offensive performances.
San Francisco scored touchdowns on its first five possessions during a 35-13 victory over Miami. Brock Purdy completed 20 of 22 passes for 287 yards and two touchdowns, added a rushing score and finished with a 149.1 passer rating. Christian McCaffrey scored twice, giving him 100 total touchdowns in his career, and the 49ers did not punt until the fourth quarter.
That followed a 27-7 opening victory over the Rams in Australia. The main concern for San Francisco is its receiving depth, with Demarcus Robinson and Mike Evans joining a wounded positional group that features multiple players
on injured reserve. The 49ers finished the Miami game with a reduced group that included Deebo Samuel, Jacob Cowing and KhaDarel Hodge, making the week's practice reports important for determining Purdy's available options.
Arizona opened the season with a 26-14 victory over the Chargers. Jacoby Brissett passed for 277 yards, Trey McBride caught nine passes for 95 yards and a touchdown, and rookie running back Jeremiyah Love scored on his third NFL carry. The offense was far less effective in a 31-7 loss to Seattle. Brissett threw for only 95 yards with one touchdown and one interception, while McBride accounted for eight receptions but just 41 yards.
Arizona will seek more production beyond short throws to McBride, particularly when facing a San Francisco offense capable of creating early separation. Establishing Love and the running game could help the Cardinals control possession and reduce the number of opportunities available to Purdy and McCaffrey.
49ers vs Cardinals odds, moneyline, over/under
Opening lines:
- Spread: 49ers -8.5
- Moneyline: 49ers -400; Cardinals +370
- Total: 47.5
Get the edge with our exclusive NFL betting picks
Cardinals at 49ers score predictions
Adam Kaufman: 49ers 34, Cardinals 17
San Francisco has scored touchdowns on nine of its first 12 possessions this season, while Arizona generated only 95 passing yards against Seattle. Granted, Jacoby Brissett should be better than that this time around, but it's difficult to envision the Cardinals rediscovering the offense that helped upset the Chargers in Week 1. The 49ers are simply too good, even with a banged-up receiving corps. San Francisco destroyed Miami last week, scoring touchdowns on its first five possessions before essentially calling off the dogs with a 35-6 lead in the fourth quarter. This feels similar. Demarcus Robinson's high-ankle sprain and Mike Evans' hip injury are worth monitoring, but Kyle Shanahan still has Brock Purdy, Christian McCaffrey, Deebo Samuel and George Kittle. Arizona doesn't have enough answers.
Michael Middlehurst-Schwartz: 49ers 30, Cardinals 20
The feel-good vibes around the Cardinals dissipated a little when the Seahawks put the NFC West cellar-dwellers back in their place following Week 1's surprise win over the Chargers. Week 3 could be more of the same for Arizona. Though the offense shouldn't be as stifled as it was against Seattle, the Cardinals will probably have a hard enough time getting Brock Purdy and San Francisco's run game within its grasp.
Nate Davis: 49ers 27, Cardinals 20
You probably wouldn't think Niners coach Kyle Shanahan has had all that much trouble with the Cards through the years. Turns out he's 9-9 against Arizona, which is just another indicator of how especially competitive divisional matchups tend to be. But, despite the injuries to the 49ers' receiving corps, let's not overthink this one – especially given San Francisco has, by far, the league's biggest point differential (+42) through two weeks.
Richard Morin: 49ers 24, Cardinals 13
It was a rough assignment for the Cardinals in Week 2 against the Seahawks, the reigning Super Bowl champions and owners of perhaps the NFL's most devastating defense. The 49ers are no slouch, either. Maybe it's just me, but I don't see much runway for Arizona to produce a different result in Week 3. The Cardinals' rushing talent remains intriguing, but it was unable to break through the Seattle unit. Perhaps more opportunities exist against San Francisco, but it's not enough for a winning result.
Where to watch Cardinals at 49ers
- Matchup: 49ers vs. Cardinals
- Date: Sept. 27
- Time: 4:05 p.m.
- Venue: Levi's Stadium
- Location: Santa Clara, California
- TV: Fox
NFL Week 3 picks and predictions
- Falcons at Packers
- Chargers at Bills
- Raiders at Saints
- Patriots at Jaguars
- Texans at Colts
- Seahawks at Commanders
- Chiefs at Dolphins
- Jets at Lions
- Bengals at Steelers
- Vikings at Buccaneers
- Titans at Giants
- Cardinals at 49ers
- Panthers at Browns
- Ravens at Cowboys
- Rams at Broncos
- Eagles at Bears
This article originally appeared on USA TODAY: Cardinals at 49ers: Predictions, picks and odds for NFL Week 3 game
Advertiser disclosure: USA TODAY may earn a commission when you sign up through links on this page. Commissions never influence our editorial coverage or rankings. Offers and odds were accurate at publication and are subject to change; terms apply — see the operator’s site. This is general information, not betting, legal or financial advice. To the fullest extent permitted by law, USA TODAY is not liable for losses arising from your use of it.
Must be 21+ (18+ where permitted). Sports betting and casino gaming are not legal everywhere; complying with the laws where you are located is your responsibility. Gamble only with funds you can afford to lose. Gambling problem? Help is available 24/7 — call or text 1-800-GAMBLER, or call the National Problem Gambling Helpline at 1-800-MY-RESET. State helplines and responsible gaming resources.
