Broncos vs. Cardinals Prediction, Spread, NFL Picks – Sunday, October 25

Week 7 of the 2026 NFL season features an intriguing interconference matchup as the Denver Broncos travel to State Farm Stadium to face the Arizona Cardinals, featuring a 4:05 p.m. ET kick off on CBS. For Sunday, October 25's matchup, the Broncos are 4.5-point favorites on the spread, via PrizePicks.

Denver enters Sunday's game at 4-2, relying on an impressive defense to build a winning record despite inconsistent offensive production. Arizona enters at 2-4 but is coming off an impressive road win over the Rams.

Below, we break down the matchup for our Broncos vs. Cardinals prediction, capped by player projections for PrizePicks.

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Broncos vs. Cardinals Prediction, Spread, Over/Under – Sunday, October 25

Denver enters Sunday's matchup as a 4.5-point road favorite, returning a 1.42x payout if they win outright.

Here are the full payouts for the Broncos vs. Cardinals game. PrizePicks data is live at the time of writing and is subject to change.

Make your Broncos vs. Cardinals prediction on the spread on PrizePicks.

Unless otherwise noted, data used in this article is from Sumer Sports, PFF, and Pro Football Reference.

The Broncos have averaged only 19.0 points per game while allowing 18.0 on defense. Denver ranks 29th in offensive success rate (37.5%) compared to ninth in defensive success rate (41.6%). The defense may receive a significant boost with CB Pat Surtain II (ankle) questionable on Sunday.

Arizona, meanwhile, sits at 2-4 and has struggled to find consistency on both sides of the ball, averaging 21.0 points per game while surrendering 29.7.

Denver's offensive production remains a big concern. The Broncos have totaled just 174.8 passing yards per game, and QB Bo Nix has thrown for 1,049 yards and 6 TDs through six contests.

However, Arizona's defense presents an intriguing bounce-back opportunity for him and this offense. The Cardinals have given up +0.27 EPA per dropback, ranking near the bottom of the league.

Arizona's offense has shown promise under QB Jacoby Brissett, who's thrown for 1,328 passing yards and 9 TDs. However, his 6 INTs have limited the unit's consistency. The Cardinals will need to protect the football against a Denver defense that has shown it can generate pressure and capitalize on mistakes. 

The Cards' ability to establish its running game and avoid obvious passing situations could be particularly important against the Broncos' pass rush. But that could be easier said than done, with Arizona RB Jeremiyah Love missing his second consecutive game from an ankle injury.

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Broncos vs. Cardinals Prediction on Spread – 10/25/26

Here are the key stats and predictions behind our Denver Broncos vs. Arizona Cardinals spread prediction for Sunday afternoon.

• The Broncos rank 25th in offensive EPA per play (-0.079) and 29th in offensive success rate (37.5%). 
• They have also converted just 32.1% of third downs, ranking 30th in the NFL. These numbers suggest Denver struggles to sustain drives consistently, creating a real risk that its offense won't generate enough points to pull away for a cover in Week 7.
• The Cardinals sit 11th in offensive success rate (46.4%). Arizona has also averaged 66.5 offensive plays per game (fourth-most), while Denver averages just 56.5. If the Cardinals keep generating first downs and extending possessions, they can limit Denver's offensive opportunities and keep their own weak defense off the field.
• Arizona ranks 30th in defensive EPA per dropback (+0.249). However, Denver's offense ranks just 24th in passing EPA per dropback (-0.101) and 30th in explosive passes of at least 15 yards (9.3%).
• The Broncos rank 28th in EPA/rush allowed (-0.01). This could give Arizona a direct path to offensive success by running the ball and sustaining long, methodical drives.
• This game features a promising pairing: home dogs (+4.5) in low total games (43.5).

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Broncos vs. Cardinals Picks, Player Stats for PrizePicks – 10/25/26

Here are two Broncos vs. Cardinals player picks to consider on PrizePicks for Sunday afternoon, featuring Bo Nix and Jacoby Brissett.

Broncos QB Bo Nix vs. Cardinals: 221.5 Pass Yards

• Arizona has been one of the NFL's worst defenses against the pass, ranking 30th in defensive EPA per dropback, 30th in passing success rate allowed, 31st in yards per pass attempt allowed, and 32nd in passer rating allowed. 
• The Cardinals are giving up 8.6 yards per attempt and a 116.5 passer rating, giving Nix by far his most favorable matchup of the season.
• Arizona has been particularly vulnerable to explosive passing plays this season, allowing a 19.1% rate of completions gaining at least 15 yards (second-highest) and an 11.2% rate of completions gaining at least 20 yards (30th).
• The bottom line: Nix averaged 231.0 passing yards per game last season and added an elite receiver in WR Jaylen Waddle. He gets arguably the best matchup for a passing offense against Arizona, and it’s now or never for Nix to start playing as he has in the past.

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Cardinals QB Jacoby Brissett vs. Broncos: 226.5 Pass Yards

• Brissett is averaging 221.3 passing yards per game. That leaves him slightly below this projection before accounting for the difficult matchup against Denver.
• The Broncos have recorded 18 sacks through six games. That pressure could disrupt Arizona's passing game and force Brissett into difficult situations before his receivers have time to get open.
• Brissett's turnover problems may become especially costly if Denver consistently generates pressure. Instead of allowing Arizona to sustain long drives, the Broncos could force hurried throws, incompletions, and sacks that stall possessions.
• Arizona would be wise to lean on its running game and find a favorable matchup. The Broncos have operated as an extreme run-funnel this season, ranking fifth in EPA/pass and 28th in EPA/rush.
• Running the ball can also help sustain drives and keep the beleaguered defense off the field.

Add Jacoby Brissett to your PrizePicks lineup now.

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Sunday's matchup presents an interesting contrast between Denver's struggling offense and Arizona's struggling defense. The Broncos have done enough to build a winning record, but their inconsistent offense could make it difficult to cover a spread of more than a field goal on the road.

Don't wait until kick off — make your Broncos vs. Cardinals picks on PrizePicks now for Week 7 and earn real money if you're right.

Pick players, predict More or Less on their stats, and cash in if you're right. With Team Picks, you can make predictions on game winners, spreads, and over/unders, now available on PrizePicks.

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