Giants vs. Bills Prediction, Odds & Expert Picks: NFL Preseason Week 1

Who comes out on top when the new-look Giants square off in an intrastate battle against the Bills?

Mike Spector

Last Updated: August 9, 2025 12:27 PM EDT • 4 minute read

Giants vs. Bills Prediction, Odds & Expert Picks: NFL Preseason Week 1 — Pictured: New York Giants wide receiver Malik Nabers talks with quarterback Russell Wilson as we make our best Giants vs. Bills prediction. Photo by Vincent Carchietta via Imagn Images.

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Two teams from the same state meet in the first week of the NFL preseason as the Buffalo Bills host the New York Giants, and we have you covered with our Giants vs. Bills prediction.

This game kicks off from Highmark Stadium in Orchard Park at 1 p.m. ET (NFL Network) on Saturday, and we offer our best ATS and O/U picks (the Bills are one-point favorites with an O/U of 36.5 points). Be sure to check out the rest of our NFL preseason Week 1 predictions from our best handicappers.

🏈 Giants vs. Bills predictions & expert picks

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✅ Against the spread pick: Giants +1.5 (-115 via FanDuel) ⭐⭐⭐⭐
✅ My best bet: Under 36.5 (-110 via BetMGM) ⭐⭐⭐⭐

🔮 Giants vs. Bills ATS prediction

🗽 Giants +1.5 ⭐⭐⭐⭐

📊 Best odds: -115 via FanDuel ($10 to win $8.70)
🔢 Implied probability: 53.49%

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The Giants flipped from 2.5-point underdogs earlier in the week to 1.5-point favorites, and bettors can find great value on their preferred side with each team catching points depending on the sportsbook.

New York has a diverse mix of veterans (Russell Wilson and Jameis Winston) and a flashy rookie (Jaxson Dart) in its quarterback room. I am sure former Bills OC and Giants head coach Brian Daboll is more concerned that Buffalo’s staff is about to learn what he has with an entirely new group from last year.

The Bills seemingly do not have much open competition for many spots on their 53-man roster. But their injury news thus far is concerning, especially on the offensive line, where the team worked out four new interior linemen this week alone.

With the Buffalo likely not playing many people that will heavily impact this year’s roster, the line jumping the fence to New York, even if only for a short time, seemed justified.

📖 Check out our 2025 NFL preseason betting guide for the best betting strategies and full NFL preseason schedule.

💰 Giants vs. Bills best bet

⬇️ Under 36.5 ⭐⭐⭐⭐

📊 Best odds: -110 via BetMGM ($10 to win $9.09)
🔢 Implied probability: 52.38%

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While Buffalo’s defensive injuries have piled up throughout the week, I am more concerned with its injuries at the skill positions. Three wide receivers (Khalil Shakir, Curtis Samuel, and Kaden Prather) are all dealing with injuries, and there will likely not be much desire to push its backup running backs with starter James Cook in the middle of contract negotiations.

I expect a heavy dose of Shane Buechele at quarterback for Buffalo, with Mitchell Trubisky and Mike White having plenty of games as starters under their belts. Meanwhile, Giants rookie Jaxson Dart went 9-of-15 passing with an interception in team drills on Wednesday, and has not given any assurance that he will limit turnovers in live game action.

BetMGM is the only one of the top sports betting sites offering a total of 36.5 (others are at 36) with the standard -110 juice to back the Under, which is juiced as -118 at competing shops.

📊 Giants vs. Bills odds

Live updated odds from our best live betting sites. Follow the latest NFL scores for line history and matchup info.

🪧 Giants vs. Bills opening odds:

Giants: +2.5 (-110)
Bills: -2.5 (-110)

🚑 Giants vs. Bills injuries

📈 Giants vs. Bills betting insights

Here are some betting insights from BetMGM just prior to kickoff:

This game is the most-bet contest of the day in terms of tickets
The Bills covering -3 is getting the most tickets as well
The Over on 36.5 is also drawing the most action across BetMGM

🏆 NFL betting odds pages

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Written by:
Mike Spector

Mike started in the sports writing industry in July 2019, and gained a lot of followers in his first year after finishing with the No. 2 overall record in an annual NFL betting competition, which made picks against the spread, and from an Over/Under and moneyline perspective. Mike is an avid fan of the NFL, MLB, tennis, and all college sports. In his opinion, March Madness is the best sporting event there is, and he's especially euphoric starting with conference tournament time in college basketball. Mike's a big advocate of "fading the public" and making plays that are contrarian, constantly citing that "there are reasons why they have those big shiny buildings in Las Vegas." When making wagers, Mike leans on his NFL experience and always scours the best odds at all of the major sports betting sites, where he mostly sifts through DraftKings, FanDuel, BetMGM, and bet365. He's tried several others and is of the firm belief that bettors should not just stick to one sportsbook, as there is always likely better value to be had with the same wager. In addition, while Mike received his undergraduate degree from Villanova University, he has no issue betting against the Wildcats when it comes to college basketball wagering, and suggests other bettors should always put their “head” before their “hearts.”

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