Santa Clara, CA – September 18, 2025
The San Francisco 49ers (2-0) remain unbeaten after knocking off the New Orleans Saints, 26-21, in Week 2. Now, they return to Levi’s Stadium for a crucial NFC West battle against Kyler Murray and the Arizona Cardinals (1-1).

The road doesn’t get any easier for San Francisco. Their first two games were physical slugfests, and the Cardinals enter Week 3 hungry to prove they can compete in the division after splitting their first two matchups.
Fans will recall that last season, the 49ers dominated Arizona in both meetings, including a 38-10 rout at Levi’s. Christian McCaffrey totaled over 150 yards from scrimmage in that game, while Nick Bosa and the defense recorded four sacks. But divisional games are always unpredictable — and Murray’s dual-threat ability keeps Arizona dangerous.
The question now: can Purdy, McCaffrey, and the 49ers’ defense keep their perfect start alive on Sunday?
Game Info: 49ers vs. Cardinals, Week 3
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When: Sunday, September 21, 2025 – 4:25 p.m. ET (1:25 p.m. PT)
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Where: Levi’s Stadium, Santa Clara, CA
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TV: FOX
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Streaming: NFL+, YouTube TV, Fubo
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Radio: KNBR 680 AM / 107.7 The Bone
Local 49ers fans can also catch pre-game and post-game coverage on NBC Sports Bay Area.
Sportsbooks currently list San Francisco as 6.5-point favorites heading into the matchup.