San Francisco 49ers vs Arizona Cardinals Prediction, 11/16/2025 NFL Picks, Best Bets & Odds Week 11

Game: San Francisco 49ers vs Arizona Cardinals

Date: Sunday, November 16, 2025

Location: State Farm Stadium in Glendale, AZ

TV: FOX

Odds-Point Spread: Cardinals (+2.5)

Total-Over-Under: 49

State Farm Stadium is the place where the Arizona Cardinals (3-6) will try to defeat the San Francisco 49ers (6-4) on Sunday. Arizona opens this contest as 2.5-point underdogs from oddsmakers. The total is set at 49.

The San Francisco 49ers step on the gridiron 6-4 this season. When they last took the field, the 49ers played the Los Angeles Rams and walked away from this one with a loss by a score of 42-26. Mac Jones went 33-39 with 319 yards passing and 3 touchdowns. He had a QB rating of 115.7 and ended the game with 1 interception. Kendrick Bourne held an average of 19.0 yards per catch by totaling 19 yds on 1 reception. Christian McCaffrey led the offense in rushing for the 49ers with 12 totes for 30 yds (2.5 yds per carry). For the game, they ran 60 plays which totaled 393 yds. The San Francisco 49ers ended up running the ball 21 times and recorded 74 yards, which came out to an average of 3.5 yards per tote. Against the run, the 49ers conceded 126 yds on 30 tries, which averages out to 4.2 yds per rush allowed. San Francisco surrendered 24 completions on 36 attempts for a total of 275 yards, and a completion percentage of 66.7%.

The 49ers have collected 3,562 yards over the course of this season. San Francisco has amassed 139 1st downs as an offense, and they have been hurt by 61 infractions for 467 yds. If you analyze scoring touchdowns, San Francisco has recorded 17 passing TD's and 6 rushing TD's. They have coughed up the ball 15 different times (10 interceptions and 5 fumbles). As a unit, they're sitting at 94.8 running yds which has them sitting 27th in football. If you analyze scoring touchdowns, the San Francisco 49ers average 22.0 points per game.

If you analyze pass yards, the 49ers have allowed 2,288 total yards, which ranks them at 26th in football. They have yielded 228.8 yards per contest via the pass, and are allowing a completion percentage of 67.8%. Altogether, they have given up 1,106 running yards through 10 matchups on the year. They have conceded 19 touchdowns via the pass, along with 7 touchdowns via the rush. All in all, they are granting 339.4 yards per outing, which has them sitting 21st in football. Opposing teams are running for an average of 4.2 yds per attempt on the ground and 110.6 running yds per game for the year. The 49ers sit 15th in the league with reference to their defensive abilities, allowing 23.0 points per game.

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The Cardinals head into this matchup 3-6 on the year. In their last game, the Cardinals took a defeat with a final score of 44-22 against the Seattle Seahawks. Jacoby Brissett (2 touchdowns) finished the game with 258 yards on 22-44 through the air while his quarterback rating was 83.3. He didn't toss any picks and his Y-A was 5.9 yds. Emari Demercado had the best day in terms of receiving for the Cardinals, hauling in 3 footballs for 40 yds (13.3 yds per reception). Zonovan Knight carried the football 10 times for 28 yards, ending the contest with 2.8 yards per carry for Arizona. The Cardinals finished the contest with a total of 335 yards while running 68 plays (4.9 yds per play). Arizona rushed for 5.6 yds per attempt, finishing with 129 yds on 23 attempts. Arizona allowed 46 running attempts for 198 yds (4.3 yards per rush). The Cardinals pass defense gave up a completion rate of 83.3%, surrendering 174 yds on 10 for 12 through the air.

The Arizona Cardinals hold an average of 316.3 yds per contest, which is good for 21st in football. They have an average of 113.4 rushing yds per contest, and have rushed for 1,021 yards. They have allowed 4 picks while surrendering 6 lost fumbles, and have been able to earn 107 first downs offensively. The Arizona offense has conceded 440 total yards on 61 violations, which has them ranking 20th in the league with reference to helping out the other team. On the campaign, the Cardinals have earned 1,826 passing yards and hold an average of 202.9 passing yards per game, ranking this team at 21st in the NFL. When analyzing their scoring prowess, the Cardinals sit 20th in the league, by tallying 22.4 points per game.

The Cardinals are giving up 23.9 PPG, which is good for 19th in football. They have allowed 10 touchdowns by way of the pass along with 225.3 pass yards per outing, which ranks them at 20th in football. Arizona has allowed a total of 1,027 running yds (114.1 yards per outing), and 9 touchdowns to runners on the campaign. The Cardinals defense has taken the field for 572 plays from scrimmage, which ranks them at 19th in the league. The defense has amassed 13 takeaways (7 forced fumbles and 6 INTs) over the course of this season. All in all, they have surrendered 215 pts.

Who will win tonight's 49ers-Cardinals NFL game against the spread?

Guy's Pick: Take the 49ers -2.5

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