The NFL has made it clear that it intends to engineer memorable matchups for the opening week of the season, saving its prime-time slots for marquee teams. Sometimes, though, the most captivating results come from unexpected games.
Might there be the equivalent of the New England Patriots' 2024 toppling of the Cincinnati Bengals ahead this fall? The league has mostly embraced level matchups for the opening week, but there are still a few opportunities for a true surprise.
With the full 2026 NFL schedule released, we took a look at the three seemingly most lopsided matchups and evaluated each on its upset potential on a scale from 1-10.
Clemson Tigers offensive lineman Blake Miller is selected by the Detroit Lions as the No. 17 pick during the NFL Draft at Acrisure Stadium on April 23 in Pittsburgh.
Saints at Lions
Coming off a disappointing 9-8 campaign, the Lions have the look - and favorable schedule setup - of a team poised to make a postseason return. But there's plenty for Detroit to sort out in the early going. A reshuffled offensive line will flip All-Pro offensive tackle Penei Sewell to Jared Goff's blind side, allowing first-round rookie Blake Miller to step in at right tackle. There's also a new play-caller coming from the outside in offensive coordinator Drew Petzing.
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The Saints, who won four of their final five games last season, could capitalize on any early friction. Brandon Staley's defense made significant strides over the course of last year, finishing the season sixth in yards allowed per play. With sizable investments in running back Travis Etienne Jr. and offensive guard David Edwards, a languishing ground game could come to life. And with first-round receiver Jordyn Tyson in tow, an aerial attack helmed by promising second-year signal-caller Tyler Shough should be a good deal more threatening to opposing defenses.
UPSET POTENTIAL: 5. Detroit faceplanted in its opener last season, with issues along both lines coming to the forefront. New Orleans isn't nearly as formidable on either side as the Green Bay Packers were last September, but the Lions still might require some time to coalesce. The Saints would need several elements to break their way to pull off the upset, including an advantage in the turnover battle to offset issues with the pass rush and secondary. But Kellen Moore's team could be a bit overlooked heading into the coach's second year, and this group could have enough to keep pace with the Lions.
Cleveland Browns defensive end Myles Garrett, left, tries to get past Pittsburgh Steelers guard Spencer Anderson as quarterback Aaron Rodgers looks to throw during the second half of a Dec. 28 game at Huntington Bank Field in Cleveland.
Browns at Jaguars
There's a good deal of familiarity between these two regimes, which last April orchestrated the draft trade centered on Travis Hunter Jr. and later reconvened for a swap of cornerbacks at the trade deadline. Little else, however, binds Jacksonville and Cleveland, with the former having made a nine-win improvement in coach Liam Coen's first year while the latter continued to flounder.
Might new coach Todd Monken help the Browns chart a new course right away? It's a tall order, but change should do the offense some good, even if the outlook at quarterback remains inauspicious. Maintaining composure will be a key early challenge for a unit with so many new pieces, and the Jaguars - who ranked second in the NFL with 31 takeaways in 2025 - will surely pounce on any missteps. Cleveland's defense could be more volatile after Jim Schwartz's departure, but Myles Garrett's presence alone will continue to alter game plans.
UPSET POTENTIAL: 2. A Week 1 road triumph against a playoff team seems mighty lofty for a team that's heavily reliant on first- and second-year players. Though Jacksonville's defensive front doesn't inspire much fear, a Cleveland offensive line featuring five new starters likely won't find its footing right away. And with a well-orchestrated rushing attack, the Jaguars seem less prone than other teams to having their game plan wrecked by Garrett.
Los Angeles Chargers coach Jim Harbaugh, left, and father Jack Harbaugh watch during offseason workouts on May 11 in El Segundo, Calif.
Cardinals at Chargers
The only thing rougher for Arizona than its social media team's schedule release video was the opening slate itself. The NFC West cellar-dweller's September setup features trips to Los Angeles and San Francisco sandwiching a home date with the defending champion Seattle Seahawks. A rout by the Chargers could be a sign of what's in store for the Cardinals this season.
If Arizona can pull off the upset, it would constitute the clear stunner of Week 1. The Chargers will be breaking in two new coordinators and still have some uncertainty on their interior offensive line. Yet it would require a massively uncharacteristic slip-up for Jim Harbaugh's group to falter here. Despite showing some early fight last season in their 2-0 start, the Cardinals are still saddled with one of the league's most lackluster rosters.
UPSET POTENTIAL: 1. This will be the chalk pick in any survivor pool, and with good reason. Though the Cardinals might try to lean on No. 3 overall pick Jeremiyah Love to mitigate the shortcomings behind center, Los Angeles' defense seems unlikely to crack after ranking second in red-zone touchdown percentage allowed in each of the last two years. Meanwhile, new play caller Mike McDaniel might not even need his new group to be fully up to speed in order to handle a defense short on difference-makers. The Chargers faltered last season in early-season matchups against the New York Giants and Washington Commanders, so another slip-up can't be fully ruled out. But it seems clear that any favorable outcome for Arizona would hinge on Los Angeles erring on several fronts.
