On the other side, Arizona Cardinals quarterback Jacoby Brissett is playing steady, consistent football. He has thrown for 200-plus passing yards in five straight games. In Week 1 he completed 73.0% of his throws for 277 yards, one touchdown, and zero interceptions against the Chargers. He is not flashy, but he protects the ball, and he leans heavily on one of the most productive tight ends in the league. Trey McBride caught 9 of 13 targets for 95 yards and a touchdown in Week 1 with a 33% target share. His career line against Seattle stands at 64 receiving yards per game across seven games, with his most recent meeting against this defense producing 9 catches for 127 yards and a touchdown. That history is not a coincidence. As Sports Illustrated noted heading into Sunday: "For Seattle, they have to take Arizona seriously not only due to the Cards' performance in Week 1, but also the absence of Sam Darnold."

The injury report is messy on both sides. Arizona lists both starting guards Isaac Seumalo (shoulder) and Isaiah Adams (knee) as questionable alongside defensive tackles Andrew Billings (knee) and Roy Lopez (groin). Williams is out with an Achilles injury, with Denzel Burke stepping into the starting role. For Seattle, Zach Charbonnet remains unavailable at running back, safety Ty Okada is out, and Nick Emmanwori is questionable. Neither team is fully healthy, which matters when margins are measured in field goals. A game that looked like a divisional showdown between two legitimate playoff-caliber rosters now carries significant uncertainty on both sides.

Both defenses are real. Seattle's unit recorded 47 sacks and 25 takeaways last season and has already generated 3 interceptions while allowing just 10 points through one 2026 week. Arizona held the Chargers to 14 points in Week 1. Macdonald enters this game 4-0 all-time in head-to-head matchups against Jonathan Gannon. That coaching edge is genuine, but the question is whether Lock gives Macdonald enough offensive production to pull away cleanly. Check out the full NFL slate for the rest of Sunday's card.

• Drew Lock replacing Darnold is a material offensive downgrade. Seattle's offense scored 13 points in Lock's Week 1 start against New England. A road divisional game is not the setting to expect a breakout, and a spread that requires Seattle to win by a field goal or more is a difficult number for this offense to cover.
• Trey McBride has averaged 64 receiving yards per game against Seattle across seven career meetings. His most recent game against this defense produced 9 catches for 127 yards and a touchdown. He has posted 62-plus receiving yards in three straight games entering Week 2, commands a 33% target share, and has operated at a snap rate between 80 and 96% this season. He is Arizona's offense.
• Jacoby Brissett has thrown for 200-plus passing yards in five straight games. His Week 1 performance, 27-for-37 for 277 yards with zero turnovers, shows a game manager who does not lose games on his own. His career line against Seattle is 188 passing yards per game across three meetings, and his most recent matchup with this defense produced 258 yards and two touchdowns.
• Smith-Njigba is the Seattle passing game when Lock is under center. He accounted for 122 of Seattle's 188 total passing yards in Week 1 on 8 of 11 targets, and he carries a 33% target share and a 0.80 WOPR. His career average against Arizona is 68 receiving yards per game across six games. With Garrett Williams out and Denzel Burke filling in at cornerback, Arizona's coverage is softer than usual.
• Macdonald is 4-0 head-to-head against Gannon, and Seattle's defensive infrastructure is legitimate regardless of who lines up at quarterback. The contrarian case for Seattle winning outright rests on that coaching edge and a defense that has already posted 3 interceptions in 2026, but the QB downgrade introduces enough variance to make the Seahawks ML at -194 unappealing.
• Arizona's bilateral line injuries add genuine uncertainty. Both starting guards and both starting defensive tackles are listed questionable. Brissett needs a clean pocket to sustain his completion percentage and protection from Arizona's pass rush may be compromised if those interior linemen are limited, which could allow Lock more time than expected.

The supporting case leans on Trey McBride. He has averaged 64 receiving yards per game against Seattle across seven career meetings, and nothing about this secondary with Garrett Williams out changes that calculus. Brissett has been clean and consistent, and his five-game 200-plus yard streak keeps the target volume high for his primary option. Both HIGH confidence McBride props, the receiving yards over 62.5 and receptions over 6.5, reflect a historically one-sided matchup. The Under 41.5 is a thin edge and sits within the noise threshold, so treat it as a supporting play only. The Lock passing yards under 206.5 and the same-game parlay all point to the same controlled, lower-scoring script.

The caveat is Macdonald. He is 4-0 head-to-head against Gannon, Seattle's defensive infrastructure is legitimate, and if that unit generates early turnovers and feeds Lock favorable field position, the Seahawks win this game outright without difficulty. The defensive ceiling is high enough to win despite the QB downgrade. The play here remains Arizona plus the points, but this is not a game to hammer. Back the number, acknowledge the variance, and size accordingly. For the full slate, see our NFL picks today and parlay picks.