NFL 2025: Week 4 - Picks & Predictions

Arizona Cardinals vs. Seattle Seahawks
Date/Time: September 25, 2025, 8:15 PM ET (State Farm Stadium, Glendale, AZ)

The Arizona Cardinals enter this divisional matchup at 2-1 after a frustrating 16-15 loss to the 49ers last week. They have been competitive early in the season, but their offense now faces a major challenge with the loss of running back James Conner, who is out for the year after ankle surgery. His absence leaves rookie Trey Benson and reserves like Emari Demercado to carry the load, and Arizona will need quarterback Kyler Murray to shoulder more responsibility both as a passer and on the ground. The Cardinals’ defense has shown improvement compared to recent seasons, tightening up in the red zone and on third down, but the secondary has been thinned by injuries, with cornerback Garrett Williams and defensive lineman L.J. Collier both on injured reserve. These losses could leave them vulnerable against Seattle’s versatile passing attack.

The Seattle Seahawks come into the game with a 2-1 record, fresh off a statement 44-13 win over the Saints. Quarterback Sam Darnold has been efficient running the offense, complementing a strong ground game led by Kenneth Walker III. Seattle’s defense has been a major strength through three weeks, particularly against the run—they remain one of the few teams in the league not to have allowed a rushing touchdown so far. Their front seven has controlled the line of scrimmage, and their ability to generate pressure without overcommitting blitzes has given their secondary opportunities to make plays. Offensively, the balance between Walker’s rushing and Darnold’s efficient passing has made them difficult to defend, and with Arizona thin in the defensive backfield, the Seahawks may look to push the ball downfield more than usual.

Key matchups to watch include Seattle’s run defense against Arizona’s new-look backfield. Without Conner, the Cardinals lose their most reliable chain-mover, and if the Seahawks can shut down Benson and force Murray into long passing downs, the advantage swings heavily to Seattle’s pass rush. On the other side, Arizona’s secondary depth will be tested by Seattle’s receivers, and Murray will have to find ways to exploit Seattle’s defense with tempo and creativity. Special teams could also be a factor in what projects to be a physical, divisional battle.

Given Seattle’s strong defensive form, Arizona’s mounting injuries, and the Seahawks’ ability to play balanced football, the visitors enter as slight favorites. However, the Cardinals are a resilient home team with a playmaker at quarterback who can change momentum in an instant. Still, Seattle’s depth and defensive consistency may prove too much for Arizona to overcome in a short-week matchup.

Score Prediction: Seattle Seahawks 24 Arizona Cardinals 17

Picks: Seahawks cover -3.5, under 43.5 total points

Pittsburgh Steelers vs. Minnesota Vikings
Date/Time: September 28, 2025, 9:30 AM ET (Croke Park, Dublin, Ireland)

The Pittsburgh Steelers make the trip overseas with a 2-1 record, but they arrive in Dublin carrying more questions than answers after a narrow, uneven win over New England. Their defense, long the identity of the team, is battling a rash of injuries. Edge rusher Alex Highsmith has been ruled out with a high ankle sprain, and the secondary is in flux with Joey Porter Jr. and DeShon Elliott both questionable. Patrick Queen has been limited with an oblique issue, leaving T.J. Watt and Cameron Heyward to shoulder even more of the load in the front seven. On offense, the Steelers have shown flashes of balance, but pass protection has been shaky, and the coaching staff will need to find ways to get Najee Harris and Jaylen Warren going to prevent their quarterback from being exposed against Minnesota’s defense.

The Minnesota Vikings enter this game at 2-1 as well, buoyed by a commanding 48-10 victory over Cincinnati in which all phases clicked. Carson Wentz has stepped into the starting role with poise in the absence of rookie J.J. McCarthy, showing enough efficiency to keep drives moving while leaning on the run game. Jordan Mason has provided a physical spark in the backfield, and the offensive line did a much better job creating lanes and limiting pressure last week. The Vikings’ defense is also finding rhythm, generating turnovers and even contributing on the scoreboard. This balance has allowed Minnesota to establish momentum after an inconsistent start to the season.

The matchup will hinge on two fronts. First, Pittsburgh’s ability to generate pressure without Highsmith and with a banged-up unit. Wentz has historically struggled under duress, and if Watt can wreak havoc, the Steelers can tilt the game back in their favor. Second, Minnesota’s defense against Pittsburgh’s inconsistent offense. If the Vikings’ secondary can clamp down and force Kenny Pickett (or whoever is under center) into hurried decisions, Minnesota could repeat the turnover-heavy formula that buried Cincinnati. The Steelers, meanwhile, will aim to slow Mason and prevent Minnesota from controlling tempo through the ground game.

Playing in Dublin adds an unpredictable wrinkle, as international games often come down to who handles the travel, routine disruption, and unusual atmosphere better. For a Steelers team limping into the matchup, the timing is tricky, while the Vikings seem to be gaining confidence on both sides of the ball.

Score Prediction: Minnesota Vikings 23, Pittsburgh Steelers 20

Picks: Vikings moneyline, under 45.5 total points