49ers vs Cardinals Prediction and Pick, Week 11

The Week 11 matchup between the San Francisco 49ers and Arizona Cardinals brings together two NFC West rivals who have seen their share of tight battles and surprising results over the past few seasons. Their last five meetings have been split, and three of those games were decided by a single score, showing just how competitive this rivalry has become. San Francisco holds the edge in most recent meetings, but Arizona has proven capable of shocking the 49ers when least expected — including their explosive 47-24 win last season. Both teams enter this week in very different positions. The 49ers are trying to find consistency after a rollercoaster stretch of wins and losses, while the Cardinals are fighting to stay relevant in a tough division. Statistically, San Francisco boasts a top-five passing attack but continues to struggle establishing the run, averaging just 97 rushing yards per game. Meanwhile, Arizona’s defense has been inconsistent, often bending but not breaking, allowing just 22 points per game on average. This matchup could come down to which quarterback can handle pressure better — with San Francisco’s offensive line showing vulnerability against aggressive defensive fronts, and Arizona looking to capitalize on that weakness.

The 49ers offense continues to thrive through the air, ranking fifth in passing yards at 255 per game, but their ground game remains one of the least efficient in football, averaging a league-low 3.5 yards per carry. That imbalance has put extra pressure on their quarterback to make plays in tight coverage, and while it has resulted in big yardage totals, it has also led to turnovers and missed opportunities in key moments. San Francisco ranks just 23rd in points scored per game (21.56), despite being among the most productive in total plays run. That’s a clear sign of red zone inefficiency — moving the ball well but failing to finish drives. Defensively, the 49ers remain stout, ranking 10th in points allowed (20.89), but they’ve struggled to create turnovers, forcing fewer than one interception per game. That lack of takeaways could haunt them against a Cardinals team that thrives on capitalizing when opponents fail to close. Still, when the 49ers protect their quarterback and control time of possession, they are one of the hardest teams in the NFC to beat, and their ability to generate chunk plays through the air remains their biggest advantage heading into this divisional clash.

For the Cardinals, the offense has been unpredictable but dangerous when clicking. Arizona averages 21.86 points per game, just slightly below the league average, and has shown they can move the ball effectively — particularly in the first half of games. Their balanced attack features over 110 rushing yards per game and nearly 200 passing, but consistency remains a challenge, especially in late-game situations where they rank 31st in fourth-quarter scoring. The Cardinals’ defense, however, has been a pleasant surprise, ranking 12th in points allowed and showing a knack for holding opponents under their average output. They’ve been solid against the run, giving up only about 100 yards per contest, which could neutralize San Francisco’s already shaky rushing game. The key for Arizona will be keeping their offensive rhythm through all four quarters and finding success against a San Francisco secondary that can give up yardage in chunks if not pressured. If the Cardinals can replicate their Week 18 performance from last season, when they shredded the 49ers for 47 points, they could easily pull off another upset.

✅ Our 49ers vs Cardinals Pick: 49ERS

49ers vs Cardinals Prediction: Head to Head

Date	Opponent	Score	Spread	Total	Moneyline
9/21/25	@SF	SF 16-15	SF-3.5	U47.5	SF-180
1/05/25	@ARI	ARI 47-24	ARI+1.0	O47	ARI+190
10/06/24	@SF	ARI 24-23	SF-9.5	P47	SF-425
12/17/23	@ARI	SF 45-29	ARI+6.5	O45.5	ARI+225
10/01/23	@SF	SF 35-16	SF-9.5	O43.5	SF-410
1/08/23	@SF	SF 38-13	SF-2.5	O40	SF-155
11/21/22	@ARI	SF 38-10	ARI+1.5	U49	ARI+102
11/07/21	@SF	ARI 31-17	SF-5.0	O47	SF+130
10/10/21	@ARI	ARI 17-10	ARI-5.0	U50	ARI-245
12/26/20	@ARI	SF 20-12	ARI-6.0	U48.5	ARI-278

49ers vs Cardinals Prediction: Arizona Offense

49ers vs Cardinals Prediction and Pick, Week 11, by YouWager.lv.