Nov 9, 2025; Santa Clara, California, USA; San Francisco 49ers running back Christian McCaffrey (23) runs the ball against Los Angeles Rams safety Quentin Lake (37) during the second quarter at Levi's Stadium. Mandatory Credit: Cary Edmondson-Imagn Images
Cary Edmondson-Imagn Images

49ers vs Cardinals Prediction 11/16/2025 Today’s NFL Picks

Pick details

MATCHUP San Francisco 49ers Arizona Cardinals
Team Records 6-4 3-6
Spread -3 -105 +3 -115
Moneyline -162 +136
Total Over 48.5 (-108) Under 48.5 (-112)
Where State Farm Stadium, Glendale, AZ
When Sunday, November 16, 2025
Time 04:05 PM EST
TV FOX

In this article we will formulate a 49ers vs Cardinals prediction for this NFL game on Sunday, November 16th at State Farm Stadium in Glendale, Arizona. Let’s take a look at the prediction for this week 11 matchup.

San Francisco 49ers Betting Preview

The San Francisco 49ers are 6-4 this season after they lost to the Rams by a score of 42-26 last week. San Francisco trailed 21-7 at halftime and they scored 19 points in the second half, but it wasn’t enough in the double-digit loss. The 49ers were out gained by a total of 401-393, went 3-8 on third downs, and lost the turnover battle by a margin of 2-0 in the game. Mac Jones went 33-39 for 319 yards, three touchdowns, and one interception, while Brian Robinson Jr rushed eight times for 41 yards and one score. George Kittle led the receivers with nine receptions for 84 yards and one touchdown in the loss. The SF defense recorded one sack and three tackles for loss in the game. 

Prior to that game, San Francisco defeated the Giants by a score of 34-24, but lost to the Texans by a score of 26-15 before that. The 49ers have alternated wins and losses over their last eight games and they are currently third in the NFC West standings. San Francisco has scored 22.0 points per game with 261.4 passing yards and 94.8 rushing yards per game, while they have allowed 23.0 points against per game this season. Brock Purdy sounds like he may return this week, but if he is out, we will see Mac Jones once again. Christian McCaffrey has led the offense with 626 rushing yards and 692 receiving yards with eight total touchdowns this season. 

Arizona Cardinals Betting Preview

The Arizona Cardinals are 3-6 this year after they lost to Seattle by a score of 44-22 in their last game. Arizona trailed 38-7 at halftime and never had a chance in the blowout loss, but did score 15 points in the second half. The Cardinals were out gained by a total of 372-335, went 6-16 on third downs, and won the turnover battle by a total of 3-2 in the game. Jacoby Brissett went 22-44 for 258 yards and two touchdowns, while Emari Demercado rushed four times for 64 yards. Trey McBride led the receivers with nine catches for 127 yards and one score in the loss. The Arizona defense recorded one sack and five tackles for loss in the game. 

Prior to that game, Arizona defeated the Cowboys by a score of 27-17, but lost to the Packers by a score of 27-23 before that. The Cardinals have lost six of their last seven games and they are currently last in the NFC West standings. Arizona has scored 22.4 points per game with 202.9 passing yards and 113.4 rushing yards per game, while they have allowed 23.9 points against per game this season. Jacoby Brissett has thrown for 1,118 yards, eight touchdowns, and one interception, while Trey McBride has caught 61 passes for 603 yards and six scores this year. 

Why the Arizona Cardinals will win

  • The 49ers have lost eight of their last nine games at State Farm Stadium following a loss.
  • The Cardinals have won four of their last five home games against the 49ers following a loss.
  • The Cardinals have covered the spread in six of their last seven Sunday games as underdogs.
  • The 49ers have failed to cover the spread in four of their last five games in November.
  • The 49ers have lost the first half in four of their last five games following a home loss.

Why the San Francisco 49ers will win

  • The Cardinals have lost seven of their last eight Week 11 games.
  • Brandon Aiyuk’s team has won four of its last five games with him playing against Jalen Thompson.
  • The 49ers have covered the spread in six of their last seven games as favorites following a loss.
  • The Cardinals have failed to cover the spread in five of their last six November games against NFC West opponents.
  • The Cardinals have lost the first half in 12 of their last 13 games as underdogs against NFC West opponents.

Total Points Facts

  • Each of the Cardinals’ last six Sunday games at State Farm Stadium have gone OVER the total points line.
  • Seven of the 49ers’ last eight road games against NFC West opponents have gone OVER the total points line.
  • Each of the last three games between NFC West teams have gone OVER the total points line.

Arizona Cardinals Player Prop Facts

  • Jacoby Brissett has recorded 258+ passing yards in each of the Cardinals’ last four games as underdogs.
  • Trey McBride has scored at least one touchdown in each of the Cardinals’ last four games.
  • Michael Carter has recorded 17+ rushing yards in five of his six previous Sunday appearances at State Farm Stadium.
  • Michael Carter has recorded 24+ rushing and receiving yards in each of his five previous November appearances with his team as a home underdog.
  • Michael Wilson has recorded 34+ receiving yards in each of the Cardinals’ last four games.
  • Jacoby Brissett has recorded 22+ completions in four of his last five November appearances with his team as an underdog.
  • Heading into Week 11, Josh Sweat ranks T3rd in the league for forced fumbles (3) this season.

San Francisco 49ers Player Prop Facts

  • George Kittle has scored at least one touchdown in four of his last five appearances with the 49ers as road favorites against NFC opponents.
  • Brian Robinson has recorded 21+ rushing yards in each of his seven previous appearances in Sunday games played on the West Coast.
  • Brian Robinson has recorded 24+ rushing and receiving yards in each of his 10 previous November appearances against NFC opponents.
  • Kendrick Bourne has recorded 34+ receiving yards in each of his last five November road appearances against NFC opponents.
  • Heading into Week 11, Kendrick Bourne has the most receiving yards without a receiving touchdown this season (482).

Matchup/League Facts

  • Heading into Week 11, the Cardinals have suffered the most losses when leading after Q3 this season (4).
  • Heading into Week 11, the Cardinals have suffered the most losses when leading at HT this season (4).
  • Heading into Week 11, the 49ers rank 31st in the NFL in interceptions (1) this season.
  • Heading into Week 11, the 49ers rank 31st in the NFL in turnover differential (-8) this season.

49ers vs Cardinals Prediction 

Arizona comes into this matchup trying to bounce back from their blowout loss last week against Seattle and they will be at home here. The Cardinals have lost six of their last seven games, they are starting Brissett at quarterback, and will be without Marvin Harrison Jr in this one. San Francisco has alternated wins and losses over their last eight games, which means they are due for a win if that trend continues. The 49ers might have Purdy back for this game, but their defense is getting shredded right now, so I will take the over here.

David Racey is 63-35 (64%) in the NFL this season and he is currently #1 on the NFL Leaderboard. David went 6-3 in the NFL last week and continues to be red hot. Click here for his premium plays for this week!

David Racey's Pick: Over 48.5

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