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The 49ers won the last meeting 41-22. Here is where this one stands before Week 2 is played.
The game
The Cardinals visit the 49ers on Sunday 27 September at 4:05 PM ET. The game is in Santa Clara. It is a division game in the NFC West, so both teams play each other twice this season.
The 49ers finished 2025 at 12-5 and the Cardinals at 3-14. They met twice in 2025: the 49ers won 16-15 at home, then the 49ers won 41-22 at the Cardinals.
Week 1
The Cardinals beat the Chargers 26-14 on the road, covering as a 9-point underdog. The 49ers beat the Rams 27-7 in Melbourne, a neutral site, covering as a 3.5-point underdog.
That leaves the Cardinals at 1-0 and the 49ers at 1-0. Both play again in Week 2 before this game.
The early line
The early line has the 49ers by 8.5, the median of 7 books, which range from 8 to 8.5. Books were still quoting the 49ers by 11 on 11 September. The total is 48.5, from 47.5 to 48.5 across books.
With the bookmaker margin removed, the moneyline makes the 49ers 79.8% to win. These are early prices, read on 17 September 2026 at 06:14 UTC, and Week 2 will move them.
Arizona Cardinals at San Francisco 49ers, Sunday 27 September 2026, 4:05 PM ET. Prices: US sportsbooks via Nucleus, read 17 September 2026, 06:14 UTC. 2025 results: Nucleus, checked game by game against ESPN. Every Week 3 game: NFL Week 3 odds and predictions.
