San Francisco 49ers vs Arizona Cardinals Prediction - 11/16/2025
Updated November 15, 2025
Updated November 15, 2025
The San Francisco 49ers (6‑4) and the Arizona Cardinals (3‑6) will meet in an important NFC West matchup on Sunday afternoon. The 49ers enter this game trying to catch up to the Seahawks and Rams in the NFC West, while the Cardinals try to figure things out amid a quarterback change. Before kickoff from Glendale, you can find my 49ers vs Cardinals prediction right here.
Purdy’s return is significant for San Francisco. The 49ers were 6‑4 without him and have shown resilience, but Purdy's mobility and chemistry with key targets should help the Niners in a big way. Arizona backup Jacoby Brissett is starting in place of the injured Kyler Murray. Brissett hasn't been bad in Murray's place this season. He has eight touchdown passes and just one interception so far this year. While Brissett has been steady, Harrison’s absence and a difficult opponent make this a tougher challenge for him in Week 11.
Score Projection: San Francisco 49ers 27 – Arizona Cardinals 17
Win Probability: San Francisco 49ers 58 %, Arizona Cardinals 42 %
I'll lay the field goal with the 49ers in this NFC West matchup. The Niners have to get this game to avoid falling further behind the winner of Sunday's game between the Seahawks and Rams. I think they will get the win with their starting quarterback under center once again.
Jay Sanin is the GM and Head of Sports at ATS.io. He has been writing about sports gambling since 2013, handicapping tens of thousands of sporting events. He plays sides and totals aggressively across most sports and is more selective in player prop markets. He does his own modeling across most sports, and his family is jealous of how much time he spends on his precious spreadsheets.
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