Bills vs. Browns Prediction, Spread, NFL Preseason Picks for Saturday, August 22

The NFL preseason continues with a lofty 10-game slate on Saturday, August 22. Saturday’s portion of the Week 2 schedule features the Cleveland Browns hosting the Buffalo Bills at 1:00 p.m. ET on NFL Network.

The Bills began the 2026 preseason with a 29-14 win vs. the Panthers in Week 1. Neither the Bills nor the Browns are expected to play their starters in Saturday’s contest. The Browns are favored to win, as Cleveland returns a 1.56x payout on PrizePicks Team Picks if it comes away victorious.

Below, we'll break down our Bills vs. Browns prediction and picks for Saturday’s NFL preseason game, including the spread, over/under, and key player picks for PrizePicks.

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Bills vs. Browns Prediction, Spread, Over/Under for NFL Preseason – Saturday, August 22

The Browns enter Saturday’s game as 1.5-point home favorites against the Bills, returning a 1.56x payout on PrizePicks Team Picks if they win outright.

Here are the full payouts for the Bills vs. Browns NFL preseason game on PrizePicks.

Make your Bills vs. Browns prediction on the spread or over/under on PrizePicks Team Picks—available in 36 states!

Payouts show potential returns on correct Team Picks predictions. A 2x payout returns $200 on a $100 entry. Lower multipliers reflect outcomes users are picking as more likely. Payouts are live as of writing and subject to change.

Bills vs. Brown Prediction on Over/Under for NFL Preseason – 8/22/26

Here are the key game stats and trends behind our Bills vs. Browns prediction on the over/under for Saturday's NFL preseason game. 

• Browns head coach Todd Monken revealed that he had an agreement with Bills head coach Joe Brady. If the two sides got what they wanted out of Thursday’s joint practice, then neither team would play their veteran starters on Saturday.
• Neither coach stated if they were unhappy with Thursday's reps, but it appears likely that many starters will sit out Saturday's game.
• QB Shedeur Sanders is set to start for the Browns after QB Deshaun Watson started the preseason opener.
• The Browns put up just 10 points in their preseason opener.
• The Bills scored 29 points in Week 1 of the preseason, but QB Josh Allen played the entire first quarter. Allen completed 6 of 8 passes for 111 yards and 1 TD.
• Meanwhile, QBs Kyle Allen and Shane Buechele are expected to split playing time in Saturday's contest.
• Buffalo averaged just 16.0 points per game during the 2025 preseason.
• According to SumerSports, the Browns surrendered -0.13 EPA per pass play (fourth), while the Bills ranked seventh with -0.11 EPA/pass play.

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Bills vs. Browns Picks, Player Stats for NFL Preseason on PrizePicks

Here are the top Bills vs. Browns picks to target on Saturday, August 22. Today’s NFL preseason picks for PrizePicks include QB Shedeur Sanders, WR KC Concepcion, and QB Shane Buechele.

Bills QB Shane Buechele vs. Browns: 88.5 Pass Yards

• Buechele completed 6 of 9 passes for 50 yards in the Bills’ preseason opener.
• Starting QB Josh Allen will likely sit out Saturday’s preseason game, leaving Buechele to split playing time with fellow backup Kyle Allen.
• In the 2025 preseason with the Bills, Buechele completed 36 of 46 passes for 380 yards and a TD. 
• The former SMU signal caller played sparingly with the Chiefs in 2025. He completed 7 of 14 passes for 88 yards but failed to toss a touchdown.

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Browns QB Shedeur Sanders vs. Bills: 101.5 Pass Yards

• Sanders completed 6 of 11 passes for 79 yards and an INT against the Bears in Cleveland’s first preseason game.
• According to PlayerProfiler, Sanders averaged 175.0 passing yards per game in five contests, ranking 35th among qualifying quarterbacks.
• The Bills allowed the fewest passing yards per game (156.9) during the 2025 regular season.
• Buffalo allowed its opponents to register just a 59.7% completion rate, ranking fourth in the NFL.

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Browns WR KC Concepcion vs. Bills: 23.5 Receiving Yards

• Concepcion caught 3 passes for 27 yards on 4 targets, while adding a rushing TD against the Bears last week.
• The Browns’ first-round pick registered career highs in receiving yards (919) and yards per catch (15.1) in his lone season at Texas A&M.
• Concepcion tallied a 26.7% target rate in 2025, which ranked 80th in the nation.
• The 2025 Paul Hornung Award winner was named the MVP of Thursday’s joint practice with the Bills.

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Make Bills vs. Browns Picks on PrizePicks

The Bills are expected to rest QB Josh Allen in Saturday’s preseason contest. However, the Browns are slated to keep evaluating the position, as Shedeur Sanders is expected to start. Will Sanders or Deshaun Watson separate themselves for the starting job on Saturday?

Don’t wait until kickoff at 1:00 p.m. ET—make your Bills vs. Browns picks on PrizePicks now and earn real money if you’re right.

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