One key question for the four biggest underdogs of NFL Week 1

So you're saying there's a chance.

As of Wednesday afternoon, three-fourths of Week 1 games feature a point spread of 3.5 or less.

But this isn't about them.

Below, we take a closer look at the four biggest underdogs this week and pose one question for each that could be key to pulling off an upset.

Note: Point spreads (in parentheses) provided by DraftKings.

Arizona Cardinals (+9.5)
at Los Angeles Chargers • Sunday, 4:25 p.m. ET, CBS

Can Arizona's defense get after quarterback Justin Herbert? |Let's begin by posing another question: What happens when a movable object collides with a stoppable force? 

The Chargers offensive line and Cardinals defensive line both produced poorly a season ago, and whichever maligned unit has a better game Sunday could be a determining factor. According to Pro Football Focus data, Los Angeles allowed the second-highest pressure rate (43 percent) a season ago, while Arizona generated pressure at the league's fifth-lowest rate (31.4 percent).

Tyler Biadasz, signed by the Chargers in the offseason to take over as starting center, is out for the year (torn ACL), leaving Los Angeles most vulnerable in the interior. But Arizona has its own concerns at defensive tackle. Veteran Calais Campbell led qualifying Cardinals defensive linemen in pressure rate (6.6 percent) last season, according to FTN Fantasy Stats IQ. He also finished third overall among defensive tackles in ESPN's pass-rush win rate rankings but signed with the Baltimore Ravens in free agency. Arizona replaced him with veterans Roy Lopez and Andrew Billings, who combined for 27 pressures last season, six fewer than Campbell was credited with by PFF.

Cleveland Browns (+8.5)
at Jacksonville Jaguars • Sunday, 1 p.m. ET, CBS

What does Deshaun Watson have left? | First-year Browns coach Todd Monken confounded many by naming Watson as his starting quarterback following a dreadful preseason. But despite a number of valid reasons (at least 27) to look elsewhere, he'll get the start in a battle between former Clemson national champion quarterbacks.

It's improbable, but Cleveland's only chance of winning is if Watson, who is 7-0 all-time against Jacksonville, out-duels Trevor Lawrence. 

That's a tall order. Watson hasn't played since 2024, when he ranked last among 44 quarterbacks with at least 250 snaps in success rate (36.4 percent) and No. 43 in expected points added per pass (minus-0.29), per Sumer Sports. Lawrence, as NFL Pro notes, finished last season with 19 passing touchdowns and five rushing touchdowns over the Jags' final eight games, making him only the third quarterback of the Super Bowl era to post those numbers in an eight-game span, joining former MVPs Lamar Jackson (2019) and Cam Newton (2015).

New Orleans Saints (+7)
at Detroit Lions • Sunday, 1 p.m. ET, Fox

Can Saints secondary contain Lions passing attack? | A New Orleans defensive backfield that lost slot corner Alontae Taylor in free agency will be tested against Detroit, which has had a top-three passing offense in each of the past three seasons (2023-25). Saints defensive coordinator Brandon Staley's coverages will be worth monitoring. According to NFL Pro insights, New Orleans operated in zone at the league's third-highest rate last season. Goff, meanwhile, threw for 3,425 yards and 18 touchdowns against the coverage.

Washington Commanders (+5.5)
at Philadelphia Eagles • Sunday, 4:25 p.m. ET, Fox

Do defensive additions lead to an immediate improvement? |Over half of Washington's starting defense is expected to be different from a year ago, with free-agent defensive tackle Tim Settle, outside linebackers K'Lavon Chaisson and Odafe Oweh, cornerback Amik Robertson and strong safety Nick Cross listed as members of the base 3-4 defense. Rookie linebacker Sonny Styles is another addition to the first-team unit. How quickly the talent can gel and improve upon 2025's last-place finish in total defense will not only help decide the winner of Sunday's NFC East showdown but also whether Washington, two seasons removed from an NFC Championship Game appearance, can make another deep postseason run.