Cardinals vs 49ers Prediction 9/21/25 NFL Picks Today

In this article, we will formulate a Cardinals vs 49ers Prediction for this NFL Week 3 game on Sunday, September 21st at the Levi’s Stadium. Let’s take a look at the prediction for this NFL matchup.

San Francisco 49ers Preview

San Francisco has a 2-0 record this season and is coming off a 26-21 road victory in New Orleans. Offensively, they average 21.5 points per game, which ranks 18th in the NFL. Defensively, they allow 17.0 points per game, which ranks 7th. San Francisco averages 364 total yards per game, with 98 rushing yards and 266 passing yards per game. They allow 268.5 total yards per game, 102.5 rushing and 166 passing yards per game.


Mac Jones and Brock Purdy share quarterback duties with Jones completing 26/39 passes for 279 yards and Purdy completing 26/35 passes for 277 yards. Christian McCaffrey leads the team in rushing yards, with 124, while Brian Robinson Jr. adds 53 rushing yards. Christian McCaffrey has a team-high 15 caught passes for a team-high 125 receiving yards, and has one touchdown. Ricky Pearsall has caught 8 passes for 164 yards.

Defensively, Fred Warner has a team-high 19 total tackles, 11 of them solo. Nick Bosa leads the 49ers in sacks, with two.

Arizona Cardinals Preview

Arizona has a 2-0 record this season and is coming off a 27-22 home victory over Carolina. Offensively, they average 23.5 points per game, which ranks 11th in the NFL. Defensively, they allow 17.5 points per game, which ranks 10th. Arizona averages 284.5 total yards per game, with 114 rushing yards and 170.5 passing yards per game. They allow 333.5 total yards per game, 78 rushing and 255.5 passing yards per game.

Kyler Murray leads the Cardinals with 38/54 completed passes and 341 total passing yards. He also adds 70 rushing yards. Trey Benson leads the team in rushing yards, with 83, while James Conner adds 73 rushing yards. Trey McBride has a team-high 12 caught passes for a team-high 139 receiving yards. Marvin Harrison Jr. has caught 7 passes for 98 yards, and has one touchdown.

Defensively, Budda Baker has a team-high 18 total tackles, 9 of them solo. Calais Campbell leads the Cardinals in sacks, with two. Baron Browning has one interception.

Arizona Cardinals @ San Francisco 49ers Betting Trends: Week 3

 

Why the San Francisco 49ers will win

Why the Arizona Cardinals will win

Total Points Facts

San Francisco 49ers Player Prop Facts

Arizona Cardinals Player Prop Facts

Matchup/League Facts

Cardinals vs 49ers Prediction

The Cardinals won both meetings against the 49ers last season. At home by 47-24 and on the road by 24-23, covering the spread in both. The 49ers have won the four meetings before that, but the Cardinals are 3-2 in their last 5 trips to San Fran. Over is 6-1 in their last 7 meetings.

In this Cardinals vs 49ers Prediction, the 49ers are coming as -2.5-point home favorites, with the total set at 45 points. Both teams are undefeated in this young season, with the 49ers having covered the spread in both, and are playing their first game in front of their home crowd. Arizona’s only home win this season was against a weak New Orleans squad, and while both teams have similar offensive and defensive numbers, the 49ers are far better in yards for and against. The value lies with the home team in this matchup, so take the San Francisco 49ers and lay the -2.5 points at home.

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