Bills vs Panthers Predictions | Best Bets & Odds

Last Updated: Aug 23, 2022

The Buffalo Bills will look to close out a perfect preseason in their exhibition finale against the Carolina Panthers at Bank of America Stadium on Friday.

The Bills are 2-0 after a 42-15 blowout win over the Denver Broncos on Saturday. Buffalo’s starters played about one quarter in its victory, with starting quarterback Josh Allen going 3-for-3 for 45 yards and a 28-yard touchdown pass to 2021 breakout star Gabriel Davis. Buffalo then put up 21 second-quarter points and rolled as running backs Zach Moss and Duke Johnson each rushed for two touchdowns.

Carolina, fresh off naming Baker Mayfield as its Week 1 starting quarterback, enters play against Buffalo at 1-1. The Panthers fell to the New England Patriots on Friday, 20-10, in a game where neither Mayfield nor star running back Christian McCaffrey saw reps. No. 1 receiver DJ Moore also did not play.

Here’s a look at the Buffalo vs Carolina matchup for Friday.

Bills vs Panthers Odds

Carolina’s starters are expected to play a quarter, though that likely will not include McCaffrey as he tries to remain 100 percent after an ankle injury doomed his 2021 season. Buffalo’s regulars, including Allen, are likely done for the preseason, though that has not yet been announced.

Keep track of the latest line movements in preseason Week 3 with our NFL odds.

Bills vs Panthers Implied Score

Panthers 24, Bills 18

Carolina’s starters should be able to put up points, especially given the likelihood that many of Buffalo’s impact defensive players will remain out in preparation for Week 1.

Bills vs Panthers Pick of the Day

Read more on this Buffalo vs Carolina bet below.

Bills vs Panthers Matchup

Carolina third-string quarterback Matt Corral sustained a Lisfranc injury in its loss to the Patriots that will likely cost the rookie the entire 2022 season. That means that Sam Darnold will probably play some significant time in relief of Mayfield, and P.J. Walker will probably play a bulk of the second half for Carolina. Walker has led Carolina in passing in each of its two preseason games.

Panthers coach Matt Rhule said to expect “most, if not all" starters to play, according to The Athletic, which means they will be ahead of the Bills, who are likely to focus on position battles in their final exhibition game.

The Bills are bonafide Super Bowl contenders with a loaded roster of Pro Bowlers, which is why they are likely to rest the marquee guys like Allen, Davis, Stefon Diggs, and Dawson Knox, especially as Knox mourns the death of his brother.

Bills All-Pro cornerback Tre White has still not been cleared from the physically unable to perform list, and superstar edge rusher Von Miller and safeties Micah Hyde and Jordan Poyer will probably also dodge the assignment of playing in the preseason finale since the trio hasn’t played an exhibition game.

Bills vs Panthers Prediction

Panthers 23, Bills 21

The Bills put up 35 points after Allen exited against Denver with Case Keenum lighting it up with a 16-for-18, 192-yard performance. Buffalo is averaging 34.5 points per game in the preseason, and Allen has made just three throws, which means offense shouldn’t be a problem even if Carolina’s starters play for more than a full quarter.

Still, starters vs reserves is a huge advantage, especially the longer the starters play. Mayfield, buoyed by being named the starting quarterback, should be able to put on a show for the home crowd, and the Panthers should be able to do enough to win.

Though if the Bills starting offense — which played a full half in Buffalo’s final preseason game a year ago — gets to play, that would alter this pick drastically.

Laying a touchdown in a preseason game seems nonsensical, especially in a game featuring the Bills, which has arguably the deepest roster in football. Six preseason games were decided by four points or fewer in Week 2, and taking any team to cover that much seems like a fool’s errand since the game will likely still be decided by fringe roster players.

Bills vs Panthers Bet Tips

The Bills have the second-longest active preseason winning streak, 10, which dates back to 2018. Only the Baltimore Ravens have a longer active streak (22). This will be the fifth head-to-head preseason meeting between the clubs since 2014. They’ve split the previous four, and three were decided by five points or less.

Bills vs Panthers Best Bets

Bills +6 (-110) at Caesars Sportsbook

If you’re feeling extra daring, take Buffalo to win outright at +200, since again, it is likely to at least keep the game competitive. But even though Mayfield and Moore and receiver Robbie Anderson expect to be playing, the Bills are a proud group hoping to finish undefeated in the preseason for the third straight year.

The Bills are unlikely to have the horses to win the game, given the fact their defensive standouts won’t play and their offensive stars are unlikely to either, but the way Keenum and third-string quarterback Matt Barkley have moved the ball this preseason, getting six points is a gift as our NFL pick of the day

Over 42 Total Points (-110) at Caesars Sportsbook

The Bills are leading the NFL in points per game in the preseason without Allen seeing action. The Panthers’ starters are likely to put up points against Buffalo’s reserves. No need to complicate things here.


Pat Pickens

Pat Pickens is a seasoned sportswriter who has covered pro sports since 2013 for various websites, including The New York Times,, Bleacher Report,, USA Today, the Associated Press and many others. His debut book, titled "The Whalers" about the history of the NHL's Hartford Whalers, was released in October 2021.

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