49ers vs. Cardinals 2025 Prediction, Odds, Picks - Nov 16

The San Francisco 49ers (6-4) are the favorites -- expected to win by at least a field goal, but less than a touchdown (currently -3.5) -- versus the Arizona Cardinals (3-6) in a battle of two division rivals. The expected point total for the matchup is set at 48.5.

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49ers vs. Cardinals Odds & Betting Lines

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49ers vs. Cardinals Prediction & Pick

• Pick ATS: 49ers (-3.5)
  
• Pick OU: Under (48.5)
  
• Prediction: 49ers 25 - Cardinals 20

How to Watch San Francisco vs. Arizona

• Game date: Sunday, November 16, 2025
• Time: 4:05 p.m. ET
• Venue: State Farm Stadium
• Location: Glendale, Arizona
• TV: Watch on FOX
• Streaming: FOXSports.com, FOX Sports App and FOX One (Try free for 7 days)

49ers vs. Cardinals Recent Matchups

• In their last five head-to-head bouts, San Francisco has taken down Arizona three times.
• In their last five head-to-head matchups, San Francisco has compiled 143 points against Arizona, while giving up only 131 points.

San Francisco Betting Info

• In 10 San Francisco games this season, it has five wins against the spread.
• The 49ers have not covered the spread this season (0-1 ATS) when playing as at least 3.5-point favorites.
• San Francisco games this year have hit the over on six of 10 set point totals (60%).
• When playing as the moneyline favorite, the 49ers are 5-1, picking up a victory 83.3% of the time.
• Looking at this game's moneyline, the 49ers' implied win probability is 65.8%.

49ers Stats

San Francisco's Key Players

Offense

• Christian McCaffrey has put up 626 rushing yards with four touchdowns (62.6 yards per game over 10 games). His 3.5 yards per attempt rank 44th in the league.
• He's also caught 69 passes (on 90 targets) for 692 receiving yards (sixth in the NFL) with four touchdowns. He's averaging 69.2 receving yards and 6.9 catches per game.
• Mac Jones has thrown for 2,151 yards, 13 touchdowns and six interceptions this year. He averages 268.9 yards per game and 7.4 per attempt, while completing 69.6%.
• Through eight games played, Jauan Jennings is averaging 40.5 yards and 3.5 receptions per game on the way to 324 receiving yards and 28 catches. He's been targeted 50 times, and has three receiving touchdowns.
• Kendrick Bourne has 31 receptions for 482 yards and zero touchdowns. He's been targeted 42 times in the passing game, and averages 3.4 receptions and 53.6 yards through nine games played.

Defense

• Over on the defensive side, Dee Winters has 67 tackles and five TFL in 2025. His tackle total leads the 49ers.
• Bryce Huff has 19 tackles, six TFL, and four sacks this season.
• Tatum Bethune has put up 61 tackles and two TFL this year.
• So far this season, Upton Stout has 44 tackles, three TFL, and one sack.

Arizona Betting Info

• Arizona has covered the spread five times this year (5-4-0).
• The Cardinals are 3-1 ATS when underdogs by 3.5 points or more this year.
• Games involving Arizona have hit the over on five occasions this year.
• The Cardinals have been underdogs in six games this season and won one (16.7%) of those contests.
• The Cardinals have a 38.5% chance to win this game based on the implied probability of the moneyline.

Cardinals Stats

Arizona's Key Players

Offense

• Trey McBride has put up 603 receiving yards and six touchdowns (fourth in the NFL) on 61 receptions (sixth in the NFL), while being targeted 88 times this season.
• Jacoby Brissett has 1,118 passing yards, eight touchdowns and one interception. His completion percentage is 60.9% and he averages 186.3 yards per game and 7.2 per attempt.
• Brissett also has one rushing touchdown and 82 rushing yards (seventh on the Cardinals).
• Marvin Harrison Jr. has recorded 525 receiving yards and four touchdowns on 34 receptions, while being targeted 62 times this season.
• Bam Knight has 157 rushing yards (fourth on the Cardinals) and two rushing touchdowns, while averaging 22.4 yards per game and 3.3 per attempt.

Defense

• In 2025, Josh Sweat has eight sacks to go with 10 TFL and 18 tackles over nine games. He ranks fifth in the NFL in sacks.
• Akeem Davis-Gaither has 49 tackles and two TFL. He is fourth on the Cardinals in tackles.
• Calais Campbell has five sacks (second on the Cardinals) as well as eight TFL and 26 tackles in the 2025 campaign.
• Budda Baker has totaled one TFL and 61 tackles.

FOX Sports created this story using technology provided by Data Skrive and data from Sportradar.

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