The Week 4 edition of Thursday Night Football features a couple of 2-1 division rivals, with the Arizona Cardinals hosting the Seattle Seahawks.
The game features a tight spread favoring the home side, while the total is on the low end, with each defense off to a solid start so far in 2025.
Our early Seahawks vs. Cardinals predictions and NFL picks for Thursday, September 25, lean toward the visitors in a low-scoring clash.
Seahawks vs Cardinals predictions
Here are our early thoughts on the spread and total for this week’s game. We will have a full game preview (with a best bet and SGP) later in the week.
Early TNF spread pick: Seahawks +1
I really like what I’ve seen from the Seattle Seahawks over the last two weeks, so I’ll gladly side with them against the always-inconsistent Arizona Cardinals.
Seattle has gotten a massive boost from its special teams and defense in its last two matchups. This, along with some steady offensive play, has resulted in the Seahawks outscoring the Steelers and Saints by a combined score of 75-30.
Even without the additional aid of special teams and defensive touchdowns, the Seahawks easily won the yards per play battle against both opponents. They’re moving the ball through the air especially well through three games, coming in at fourth in yards per pass attempt.
That could be the path to victory against the Cardinals, who’ve faced an extremely easy schedule of opposing QBs so far this season, with games coming against Spencer Rattler, Bryce Young, and Mac Jones. With that in mind, it’s fair to be skeptical of Arizona's strong defensive start.
Seattle has also had Arizona’s number in recent years, winning seven straight matchups, including two double-digit wins last season, where the Cardinals scored just 24 total points.
Early TNF total pick: Under 43.5 -110
Seattle’s defense is the real deal and could be on the path to being elite. Mike Macdonald is in his second season as head coach, which has enabled him to shape the team into more of his vision of a defensive powerhouse like the defenses he ran in Baltimore.
I see no reason why the Seahawks won’t limit this Cardinals offense again, just like they did last season. It’s hard to be inspired by Arizona’s attack, as they’ve topped 20 points just once while Kyler Murray is averaging just 180.6 passing yards per game.
The big mystery in this matchup is the Arizona defense, which is posting some great numbers against subpar competition. It's been a Top-4 defense on both third down and in the red zone.
While it’s fair to question the weak competition, all the Cardinals can do is play the schedule that’s in front of them, so the strong start can't be completely written off.
With Seattle's defense trending in the right direction and Arizona's quietly putting up strong situational numbers, the Under is the clear play.
Seahawks vs Cardinals odds
- Seahawks vs. Cardinals spread: Cardinals -1
- Seahawks vs. Cardinals moneyline: Seahawks -105, Cardinals -115
- Seahawks vs. Cardinals Over/Under: 43.5
How to watch Seahawks vs Cardinals
- Seahawks vs. Cardinals matchup
- Date: Thursday, September 25, 2025, 8:15 p.m. ET
- City: Glendale, AZ
- Venue: State Farm Stadium
- TV: Prime Video
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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