An exciting NFC West matchup features two 1-0 teams, with the Seahawks vs. Cardinals kicking off at 4:25 p.m. ET on FOX. Arizona has one win as an underdog; now it tries for a second dub against the defending Super Bowl champions.
According to PrizePicks, the Seahawks are 3.5-point favorites on the spread for today. Seattle will start QB Drew Lock, with QB Sam Darnold still out from a glute injury.
Below, we’ll break down our Seahawks vs. Cardinals prediction, followed by player projections via PrizePicks.
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Seahawks vs. Cardinals Prediction, Spread, Over/Under – Sunday, September 20
The Seahawks suffered a tough blow early in the 13-10 win over the Patriots when QB Sam Darnold left the game with a hip injury. Seahawks backup QB Drew Lock came in relief and threw for 187 yards and 1 TD.
The game marked the debut of first-round pick RB Jadarian Price. After averaging 5.2 yards per carry, his usage should increase, according to offensive coordinator Brian Fleury.
As long as Offensive Player of the Year WR Jaxon Smith-Njigba is on the field, the Seattle offense should be fine. He carried last season’s momentum into Week 1, finishing with 122 receiving yards and 1 TD.
The defense was the anchor of Seattle’s Super Bowl run, posting the best turnover margin (+7) and allowing the second-fewest points per game (15.3). In Week 1, the defense took over late in the game, picking off Patriots QB Drake Maye three times in the fourth quarter to help seal that win. With all the defensive starters back, this unit should remain one of the league’s best.
Going back-to-back as Super Bowl champs is very difficult, and that’s why it’s only happened twice since 2000. With most of the starters returning, the Seahawks are expected to contend with the fifth-shortest payout to win the Super Bowl (10x), per PrizePicks.
The Cardinals went to Los Angeles and beat the Chargers as a touchdown underdog. The defense shut down the Chargers’ offense, holding them to 268 total yards and 2 for 8 on third down.
Despite the Cardinals' struggles with a 1-11 record in his starts, QB Jacoby Brissett performed well. From Week 6 to Week 18 last season, he ranked first in completions (315), second in passing yards per game (283.9), and third in TDs (21).
As long as Brissett is the quarterback, Cardinals TE Trey McBride will be the focal point of the passing game. According to Hashtag Football, McBride led the team last year in target share (27.4%), red zone target share (33.3%), and end zone target share (18.4%). This high usage helped him lead all tight ends in receiving yards (1,239) and YAC (577).
That trend of heavy volume continued into Week 1, with McBride finishing third in targets (13).
The Cardinals are likely hoping they will not have to rely on Brissett’s arm as much with the backfield changes. They signed former Falcons RB Tyler Allgeier and drafted former Notre Dame RB Jeremiyah Love with the #3 overall pick in the 2026 NFL Draft.
Both running backs got their opportunities in Week 1, with Allgeier getting 17 carries and Love receiving 11. Arizona plans to rotate its backfield on Sunday afternoon.
Seahawks vs. Cardinals Spread, Over/Under – Sunday, September 20
The Seahawks are a 3.5-point road favorite with a 1.44x payout to win outright, compared to the Cardinals’ 2.63x payout.
Here are the full payouts for the Seahawks vs. Cardinals on PrizePicks, including winner payouts, the spread, and the over/under.
Make your Seahawks vs. Cardinals prediction on the spread on PrizePicks.
PrizePicks data is live at the time of writing and is subject to change.
Seahawks vs. Cardinals Prediction on Spread – 9/20/26
- The Seahawks have won nine games in a row against the Cardinals, with seven of those wins by more than 3 points.
- Opponents struggled to gain yards against the Seahawks last season, as Seattle ranked seventh in yards allowed per game (295.1).
- According to Pro Football Reference, Seattle was excellent at pressuring the quarterback, ranking sixth in pressure rate (31.0%) last season. Arizona struggled to keep pressure off the quarterback, ranking 24th in pressure rate allowed (24.5%) last season.
- According to NFL Next Gen Stats, the Seahawks rarely saw their quarterbacks get sacked, ranking ninth for sack rate allowed (5.3%) last season. The Cardinals struggled to get to the quarterback, ranking 28th in sack rate last year (4.8%).
- The new Cardinals backfield of Allgeier and Love frequently failed to gain significant yardage on the ground, finishing Week 1 18th in stuffed-run rate (14.7%). The Seahawks were excellent at containing the run, finishing eighth in stuffed-run rate (17.7%) in 2025.
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Seahawks vs. Cardinals Picks, Player Stats for PrizePicks: 9/20/26
Here are the top Seahawks vs. Cardinals picks to target on Sunday, September 20. Today’s NFL picks for PrizePicks include WR Jaxon Smith-Njigba and WR Marvin Harrison Jr.
Seahawks WR Jaxon Smith-Njigba vs. Cardinals: 81 Receiving Yards
- In Smith-Njigba’s last matchup against the Cardinals in November 2025, he recorded 93 receiving yards.
- Last year, the Arizona defense was 17th in receiving yards allowed per game to wide receivers (137.0).
- JSN led all wide receivers with 542 receiving yards on deep passes of 20+ air yards last season. In 2025, the Cardinals ranked 16th in yards allowed per game on deep passes (36.1).
- The 2025 Offensive Player of the Year finished fourth in yards after the catch last year (576). The Cardinals finished 19th in yards after the catch allowed (1,934) last year.
Add Jaxon Smith-Njigba to your PrizePicks lineup now.
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Cardinals WR Marvin Harrison Jr. vs. Seahawks: 34.5 Receiving Yards
- The Seahawks allowed the second-fewest receiving yards to wide receivers last year (1,899).
- In Harrison’s last matchup against the Seahawks in November 2025, he managed just 33 receiving yards.
- Harrison Jr. was less involved in the offense last year than in his 2024 rookie season, going from 91.8% route participation in 2024 to 78.8% last season, according to PlayerProfiler.
- The former first-round pick had minimal involvement in the game plan in Week 1, with 0 designed targets and 2 first-read targets, ranking 64th among all wide receivers.
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Make Seahawks vs. Cardinals Picks on PrizePicks
The Cardinals would love to shock the world and pull off their second consecutive upset. This matchup will be a challenge as Arizona hosts the defending champion Seahawks, who are coming off a win at home.
Don’t wait until kickoff — make your Seahawks vs. Cardinals picks on PrizePicks to win real money if you're right. Just pick your players, predict More or Less on their stats, and cash in on your predictions when you're right.
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