Seattle Seahawks vs Arizona Cardinals Odds, Picks & Prediction | Thursday Night Football TNF Betting Preview – September 25, 2025 Matchup at State Farm Stadium

Short week, divisional stakes, and a very live underdog. Seattle heads to Glendale for Thursday Night Football with momentum after a blowout win, while Arizona is regrouping after a gut-punch loss and a major injury to its workhorse back.

Game Overview

Date & Time: September 25, 2025, 8:15 p.m. ET
Venue: State Farm Stadium, Glendale, AZ
Broadcast: Prime Video
Records: Seahawks (2-1), Cardinals (2-1)

Injuries

Cardinals

James Conner (RB): Out for the season (ankle).
Will Hernandez (OL): Out (knee).
Other notable injuries: Garrett Williams (CB, IR – knee), Dante Stills (DE, questionable), Owen Pappoe (LB, questionable).

Seahawks

Devon Witherspoon (CB), Nick Emmanwori (S), and Julian Love (S) are questionable with knee, ankle, and hamstring injuries, respectively.
Zach Charbonnet (RB, foot), Christian Haynes (G, IR – pectoral).

Betting Odds & Market Data

Point Spread: Cardinals -1.5 (-110); Seahawks +1.5 (-110)
Moneyline: Cardinals -115 to -120; Seahawks +102 to +100
Total (O/U): 43.5 (-110 each way)
Early Line Movement: Opened Cardinals -2.5, now moved closer to PK/ARZ -1.5, suggesting sharp money or market correction.

Key Betting Angles

Seahawks

Seattle has covered in each of its last seven games vs Arizona and has won all seven straight-up.
Seahawks are 2-1 ATS in 2025 and are 14th in NFL offensive DVOA, trending up after scoring 30+ points in two straight games.
Seattle ranks 4th in yards per pass attempt, a clear offensive efficiency signal vs an injury-riddled Cardinals secondary.
Historical NFL trend: Road underdogs of +1 to +3 in games 2-7, where the favorite missed playoffs last year and ‘dog had 10+ wins, are 57-23-2 ATS.

Cardinals

Arizona is 2-1 ATS in 2025, but both wins came against lower-tier opposition (Saints, Panthers).
Cardinals defense rates well vs weak offenses, but faces its first premier passing attack this season.
Missing star RB James Conner, which affects rushing attack and red zone efficiency.
Cardinals have gone over the total in only 1 of their 3 games, and just once at home.

Where both teams stand right now

Seattle (2–1): The Seahawks just delivered a 44–13 demolition of the Saints, their best all-around effort of the season. Sam Darnold went 14/18 for 218 yards and 2 TDs (154.2 passer rating), rookie Tory Horton housed a 95-yard punt return a franchise record and Kenneth Walker III added two short TDs. Seattle led 38–6 at halftime and coasted.

Arizona (2–1): The Cardinals fell 16–15 at San Francisco on a field goal at the horn. Kyler Murray threw a fourth-quarter TD to Trey McBride, and Arizona even took a late lead on a safety, but the 49ers drove for the winner. More damaging: James Conner suffered a severe ankle injury and is out for the season; second-year back Trey Benson is the next man up.

Current team form & leaders

Seahawks (through Week 3):

Points per game: 29.3 (5th)
Points allowed: 15.7 (2nd)
Top pass/rush/rec: Sam Darnold 663 yards, 4 TD (QBR 63.9); Kenneth Walker III 163 rush yards, 3 TD; Jaxon Smith-Njigba 323 rec yards.

Cardinals (through Week 3):

Points per game: 20.7 (T-19th)
Points allowed: 17.0 (T-5th)
Top pass/rush/rec: Kyler Murray 542 yards, 4 TD (QBR 55.2); Trey Benson 125 rush yards; Trey McBride 182 rec yards.

Those snapshots line up with what we’ve seen on the field: Seattle’s defense is playing fast and mean (second in scoring D), and the offense is efficient enough with explosive special teams helping tilt field position. Arizona’s defense has been steady, but the offense now without Conner leans more on Murray’s playmaking and McBride’s chain-moving than on sustained, smash-mouth drives.

Matchup edges to watch

1) Seattle’s pass rush vs. Arizona’s protection
Mike Macdonald’s front is generating pressure without heavy blitz rates, and that’s usually TNF-friendly: fewer moving parts, more four-man heat. Murray can neutralize pressure with legs, but if Seattle wins on early downs without Conner’s downhill presence, those 3rd-and-longs favor the Seahawks’ rush/coverage marriage. Seattle’s scoring-defense rank (No. 2) isn’t an accident.

2) Explosives & hidden yardage
A week after a 95-yard punt return TD and a blocked punt set up points, Seattle’s special teams look like a genuine edge. Arizona’s coverage units will have to be cleaner than they were late in Santa Clara. On a total lined in the low-40s, a single special-teams splash can swing both side and total.

3) Red-zone finishers
Conner’s absence matters most inside the 20. Benson has juice, but Conner is a proven finisher with contact balance. If Arizona’s TD% dips and they’re settling for Matt Prater (or short fields needed), that invites the kind of close-game math Seattle has thrived on so far.

4) WR1s and coverage
Jaxon Smith-Njigba looks like Darnold’s comfort blanket right now (323 yards), while Trey McBride is Murray’s most consistent option (182 yards). If Witherspoon remains out, Seattle still showed it can mix and match in the secondary and survive (Derion Kendrick grabbed a pick vs. NO), but Murray’s off-script throws to McBride will be Arizona’s lever on high-leverage downs.

Handicapping the line

The market nudged off ARI -2.5 toward -1.5 after Week 3 wrapped, which makes sense: Seattle just posted a statement win; Arizona lost narrowly and lost Conner. At -1.5, you’re basically picking the winner with minimal spread tax. If you like Seattle, +1.5 is less attractive than the moneyline at a small plus price. If you like Arizona, you’re betting on Murray’s home form, a defense that’s been stingy, and Benson stepping in cleanly. I’m not quite there.

Betting card

Lean: Seahawks +1.5 (or ML +102)
The matchup tilts toward Seattle’s defense and special teams on a short week, plus Darnold’s efficiency has been real (70% completion, 4 TDs). Without Conner, Arizona’s margin for error in the red zone shrinks. I’d rather take the moneyline at a plus tag than the +1.5 given how often TNF ends up a one-score game decided late. Pick: Seahawks ML +102.

Total: Under 43.5 (light lean)
Short weeks tend to compress playbooks. Seattle is allowing 15.7 ppg (2nd), Arizona 17.0 (T-5th), and the Cards lose a drive-sustainer in Conner. If Seattle gets a lead, Macdonald can sit in split-safety shells and force long fields. I have it closer to 41. Lean: Under 43.5.

Projected score: Seahawks 20, Cardinals 17. That’s Seahawks +1.5 and Under 43.5 both live again, I prefer Seattle ML in this price range.