Seattle Seahawks vs Arizona Cardinals Prediction, Odds and TNF Picks for Today, 09/25/25

The Seahawks and the Cardinals had different results in Week 3, although not much changed about our evaluation of either team. The Cardinals lost a close game to the 49ers, but the reality is that they were vastly outplayed. San Francisco gained 355 yards to their 260, and Arizona only produced 4.1 yards per play against an above-average defense. Heading into Week 3, they had one of the easiest schedules in the NFL, which appears to be a reason behind their early success. It was yet another indictment of Kyler Murray and a pedestrian offensive product that fumbles in big spots. Even worse, Arizona lost their stalwart running back, James Connor, to a season-ending injury. On a roster with few bona fide leaders, the 30-year-old back will be missed in more ways than one.

Seattle took care of business in a very predictable outcome at home on Sunday. Jumping to a 21-0 lead in the 1st quarter, the game already felt over when the score ascended to 38-6 at the end of the 1st half. The Seattle defense was at its best — blocking punts, forcing turnovers, and wreaking havoc on a pedestrian Saints offense that only gained 284 yards, and most of that production was in garbage time. Sam Darnold and the offense cruised through all 4 quarters, never challenged or pressured at any moment during the game. The Seahawks are 2-1 and have won 2 in a row, but they’ll need to show up against more elite programs to earn our vote of confidence.

A short week always favors the home team, although both programs had to travel following their Week 3 outings. This is a very tough game to project because, according to our power ratings, the Seahawks and Cardinals are both relatively average teams. The market clearly agrees. Since Arizona is at home and needs to respond after a disappointing result last Sunday, we’ll side with them, although we’d exercise caution in wagering on either side of this contest.

Seahawks vs Cardinals prediction: Cardinals ML (-110) available at time of publishing. Playable to -120.

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