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by Lou Aguila in NFL Picks
The San Francisco 49ers will stake their spotless record against the also undefeated Arizona Cardinals on Sunday at Levi’s Stadium.
The Cardinals, who won the last two games against the 49ers, are +110 road underdogs in this match.
Current Form:
Despite losing starting quarterback Brock Purdy to multiple injuries, the 49ers secured their second win of the season after holding off the New Orleans Saints, 26-21, in Week 2. Backup quarterback Mac Jones threw for 279 yards with three TDs in the gallant win. San Francisco also trounced the Seattle Seahawks 17-13 in Week 1.
The Cardinals will also march into week 3 with a 2-0 slate after squashing the Panthers’ second-half run to hang on to a 27-22 win. Arizona also bested the New Orleans Saints 20-13 in Week 1. In that game, the Cardinals' defense made the biggest impact, conceding only one touchdown and forcing Saints quarterback Spencer Rattler to complete only 58 percent of his passes.
Key Statistics:
The 49ers rank fifth in passing yards per game (266.0), 22nd in rushing yards (98.0), and 18th in points per game (21.5). Defensively, San Francisco surrendered the 7th fewest points so far at 17.0 points per game and allowed the 6th fewest total yards per game at 268.5 yards.
The Cardinals rank 27th in the NFL in terms of passing yards (170.5), 13th in total yards (114.0), and 11th in points per game (23.5). They also rank 10th in points allowed per game (17.5).
Quarterback Matchup:
Cardinals QB Kyler Murray (383 yards, 38-54 with 3 TDs and 1 INT) vs. 49ers QB Mac Jones (279 yards, 26-39 with 3 TDs)
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Arizona Cardinals vs San Francisco 49ers Form
Table
| Teams | % | P | W | D | L |
|---|---|---|---|---|---|
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5
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1 | 2 | 2 | 0 | 0 |
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9
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1 | 2 | 2 | 0 | 0 |
Arizona Cardinals and San Francisco 49ers Latest Matches
4/6 (67%)
0/6 (0%)
2/6 (33%)
Sep 14, 2025 - NFL
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5/6 (83%)
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1/6 (17%)
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2/6 (33%)
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4/6 (67%)
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2/6 (33%)
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4/6 (67%)
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2/6 (33%)
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4/6 (67%)
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2/6 (33%)
0/6 (0%)
4/6 (67%)
Sep 14, 2025 - NFL
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Arizona Cardinals against San Francisco 49ers : Head to Head (H2H)
40 %
0 %
60 %
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Dec 17, 2023 - NFL
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Nov 21, 2022 - NFL
Arizona Cardinals - San Francisco 49ers Key Points
- Arizona is 4-2 SU in its last 6 games.
- Arizona is 7-3 SU in its last 10 games when playing on the road against San Francisco.
- San Francisco is 3-7 SU in its last 10 games.
- San Francisco is 4-12 ATS in its last 16 games at home.
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Our Arizona Cardinals vs San Francisco 49ers Prediction
With the spread set at only 2.5 points, the most logical move here is to take your chance on the underdog, the Cardinals at +110. Arizona has won the last two meetings with the 49ers, including last year’s 47-24 win. With starting quarterback Brock Purdy sidelined, the 49ers are pinning their hopes on their backup QB, Mac Jones, who threw 3 TDs against the Saints.
The problem is that the Cardinals possess way better defense than the Saints. Arizona is only allowing 4.7 yards per play this season, which is the fourth-best mark in the league. And while Jones has plenty of experience under his belt, at the end of the day, he’s not Brock Purdy. On the other hand, the Cardinals have their starting quarterback, Kyler Murray, eager to torch the 49ers again after erupting with four TDs in last year’s win over the 49ers.
Fearless Forecast: Cardinals 33, 49ers 27
Our betting prediction for the Arizona Cardinals vs. the San Francisco 49ers: the Cardinals will win
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All tips are fully researched and given in good faith, but profits cannot be guaranteed.
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