Panthers vs. Bills Point Spread: NFL Pre-Season Week 1 Odds, Prediction
Week 1 of the 2026 NFL preseason includes a matchup between the Carolina Panthers and Buffalo Bills on Saturday afternoon in Buffalo. The Panthers are looking to build on their 2025 division-winning performance, although it did not exactly take much to triumph in the NFC South. In Buffalo, it’s a new era under head coach Joe Brady after Sean McDermott was fired despite leading the Bills to a seventh consecutive playoff appearance.
Both coaching staffs have indicated that at least some of their starters will play, so there could be some high-quality football on offer – especially in the early stages of Saturday’s contest.
NFL Point Spread and Betting Analysis
The Bills come in as -3 favourites (-105) on the NFL odds, making the Panthers +3 underdogs (-115). On the moneyline, the home side is -162, and the visitors are +136. The game total is set at 38.5 points, with the over checking in at -118 and the under priced at -102.
Prior to beating Arizona 33-30 on the final play of last week’s Hall of Fame Game, Carolina had been 1-7 straight up and 0-8 against the spread in its last eight preseason games. Buffalo is 2-4 straight up in its last six preseason outings and 3-5 ATS in its last eight.
Carolina Panthers
The Panthers’ preseason opener was a fun one in Canton, Ohio. Their second game won’t draw as many eyeballs since it isn’t a standalone feature (six other games are taking place on Saturday, including two others at 1 p.m. ET), but it does come with more importance. Head coach Dave Canales has said that his starters will play somewhere between 10 and 20 snaps this weekend.
Carolina’s offence played at an extremely quick pace in the Hall of Fame Game, providing for some wild entertainment. Haynes King rushed for a game-winning touchdown as time expired, but the Georgia Tech product is now sidelined by a hamstring injury for at least one week. Still, the quarterback position should not be an issue for the Panthers. Bryce Young is expected to play in his team’s second appearance, while Kenny Pickett and Kyle Trask have plenty of NFL experience. Running back Jonathan Brooks will also be one to watch on Saturday, as he will play with the first-string offence following an extended injury layoff dating back to his college days at Texas.
Buffalo Bills
This marks the Bills’ much-anticipated debut in the brand new (and highly criticized!) Highmark Stadium. Ralph Wilson Stadium was the home of this franchise from 1973 through 2025, witnessing all kinds of success – but never a Super Bowl victory. Will a new home give Buffalo the mojo it needs to finally lift the Lombardi Trophy? Only time will tell, but it will certainly make for the kind of atmosphere on Saturday that we won’t normally see in the preseason.
Josh Allen has not often played in preseason openers (aside from one drive in 2024), but Brady’s plan appears to be different from that of McDermott. It has been confirmed that Allen will start on Saturday. Surely he won’t be out there for long, but even a brief appearance by the star signal-caller should energize both the team and the Highmark fans.
MLB Prediction: Who Will Win Panthers vs. Bills?
The Bills starters are playing, but defensive coordinator Jim Leonard confirmed that his formations and overall game plan will be entirely vanilla. With two offensive-minded coaches at the helms of their respective squads, there could be some fireworks on Saturday – just as there were in Carolina’s preseason opener. Look for the Bills to prevail in a relatively high-scoring affair in front of the home crowd at Highmark. Let’s go with Bills 24, Panthers 23.