Bills vs. Browns Prediction, Odds and Picks for Aug. 22: Buffalo a Live Dog

Written By Chris Kubala | Published at August 21, 2026
Aug 15, 2026; Chicago, Illinois, USA; Cleveland Browns quarterback Shedeur Sanders (2) passes the ball againnst the Chicago Bears during the second half at Soldier Field. Mandatory Credit: Patrick Gorski-Imagn Images

The second full week of the NFL preseason rolls on, and it brings a matchup of AFC squads when the Buffalo Bills face a Rust Belt rival in the Cleveland Browns on Saturday afternoon. We have a Bills vs. Browns prediction and odds overview here.

Buffalo is coming off a 29-14 home win over Carolina last Saturday in their preseason opener. The Bills covered the line as 2.5-point favorites in that contest. Cleveland kicked off preseason play with a 34-10 shellacking at the hands of the Bears on the road last Saturday. The Browns failed to cover the line as 2.5-point underdogs.

With all that on the table, let’s take a look at some of the other relevant information for this one ahead of kickoff.

You can follow the latest NFL Odds as kickoff approaches. Preseason numbers can shift quickly once teams reveal their plans for starters and key backups. Here's more Steelers-Jets game information, with odds via DraftKings Sportsbook:

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Bills Looked Sharp in Preseason Opener

Buffalo has a new coaching staff after parting ways with Sean McDermott. Early results were promising as the Bills’ starters were effective in their time on the field in the preseason opener against the Panthers. The starting offense scored on both possessions they were on the field. Meanwhile, the defense forced three-and-outs on Carolina’s first three possessions. The Bills rolled up a 396-201 advantage in total offense and racked up 27 first downs to the Panthers’ 18. In addition, Buffalo forced the lone turnover, setting up a fourth-quarter score that put the game out of reach.

The expectation is that if the Bills saw enough from their starters in the joint practices, their normal guys would sit here. That makes sense as Josh Allen, James Cook, DJ Moore, Khalil Shakir and company don’t need to get banged up in a meaningless preseason tilt. Therefore, Kyle Allen (14 of 16, 108 yards) and Shane Buechele (six of nine, 50 yards) expect to see the majority of the snaps under center in this one. It also gives a chance for Ian Wheeler (seven carries, 41 yards, TD) and Frank Gore Jr. (five carries, 38 yards, TD) to make an impact. On defense, rookies Kaleb Elarms-Orr and TJ Parker look to continue making a name for themselves.

Browns With More Questions Than Answers

Cleveland is starting over with Todd Monken as coach, but the preseason opener looked like the same chapter, different verse for the Browns. Their starters saw action early and gave the Browns a 10-0 advantage in the opening seconds of the second quarter. However, the wheels fell off after that as Cleveland surrendered the game’s final 34 points to lose going away. When all was said and done, the Browns lost the total offense battle by a 430-314 margin and gave up 22 first downs while picking up 13. Meanwhile, Cleveland turned the ball over three times, leading to 10 Chicago points, and recorded just one takeaway.

Like the Bills, the Browns plan to rest their starters if they see enough in joint practice. That means Deshaun Watson likely doesn’t take the field here. Instead, Shedeur Sanders (six of 11, 79 yards, INT) and Dillon Gabriel (five of eight, 23 yards, INT) will see plenty of action. Watson is the leader in the clubhouse for the starting job, though that’s nothing to write home about. Cleveland’s run game looked uninspiring against the Bears outside of rookie Davion Booth (four carries, 53 yards) in the contest. In addition, Quinshon Judkins is getting back up to speed after ending last season injured.

Bills vs. Browns Predictions

Bills +3

Even with both teams more than likely sitting their starters in this contest, one has to look deeper. Cleveland’s ones aren’t at the same level as Buffalo’s, so it only makes sense that the twos and threes aren’t at the same level either.

Joe Brady is familiar with a good chunk of his roster, having been the offensive coordinator for the last few seasons before his promotion. Meanwhile, Monken still has a lot of pieces to try to figure out in the puzzle.

Sanders and Gabriel didn’t overwhelm anyone playing in the first preseason game. While the Browns are at home, I see Buffalo threatening to win this one outright. Playing it safe, you can take the field goal on the road.

Over 37.5

Both teams went over the number in their preseason openers. The Bills put up 29 points, putting them right near their regular-season average over the last few seasons. Granted, it took a meaningless Carolina score with 20 seconds remaining to get there, but all that matters is it did.

Cleveland saw their twos and threes torched by the Bears’ backups, leading to a combined 44 points in their opener. That put the game Over the 39.5-point number set for that game.

However, this one comes in at an even lower number than each team’s preseason week one matchup. After seeing what the Browns’ backups did last week, Buffalo’s group should take advantage. Take the Over in this contest as a result.

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