The Philadelphia Eagles head to Buffalo this Sunday for a heavyweight Week 17 clash with major playoff seeding on the line. While the Eagles (10-5) have already secured the NFC East title, they are still fighting for a top-two seed. Meanwhile, the Bills (11-4) have clinched their playoff berth but need a win to keep their hopes for the AFC East crown and the No. 1 overall seed alive.

Philadelphia’s preparation for the road trip began with several key starters sidelined. All-Pro right tackle Lane Johnson (foot) and star receiver A.J. Brown (teeth) were among those who did not participate in Wednesday’s practice. While Brown is expected to play, Johnson remains a significant question mark. Defensively, the Eagles are likely to be without linebacker Nakobe Dean, though they expect a massive boost from the return of defensive tackle Jalen Carter.

The Bills enter the matchup on a four-game winning streak, led by an MVP-caliber season from Josh Allen. Allen sits just one touchdown away from becoming the fastest and youngest player in NFL history to reach 300 total career touchdowns. The collision of Buffalo’s historic offense and Philadelphia’s quest for NFC dominance has prompted analysts to perform an immediate reevaluation of Week 17 projections.

The results of these simulations were compared to updated sportsbook odds to compile the data-driven Eagles-Bills preview below.

Eagles vs. Bills betting preview

Utilize the interactive widget below to discover the latest spread, total, and moneyline odds and probabilities for the Eagles-Bills game at Highmark Stadium.

This prediction and best bet for Sunday’s NFL matchup between the Eagles and Bills is from Dimers.com, a leader in sports betting predictions.

Check out all the important details on today’s game, as well as the best odds sourced from the top sportsbooks in the country.

Game details

The key information you need before the Eagles vs. Bills NFL game.

Teams: Philadelphia Eagles vs. Buffalo BillsDate: Sunday, December 28, 2025Kickoff: 4:25 p.m. ESTLocation: Highmark StadiumNFL standings: Current NFL division standingsNFL injuries: Check the latest updates to the official NFL injury reportOdds

Odds for the key markets in the Eagles-Bills NFL battle.

Spread: Eagles +1.5 (-110), Bills -1.5 (-104)Moneyline: Eagles +102, Bills -110Total: Over/Under 43.5 (-105/-112)

The odds and lines presented in this article are the best available from selected sports betting sites at the time of publication and are subject to change.

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Expert prediction: Eagles vs. Bills

Leveraging cutting-edge data analysis and machine learning, the experts at Dimers have performed 10,000 simulations of Sunday’s Eagles vs. Bills matchup.

According to Dimers’ independent predictive analytics model, the Bills are more likely to defeat the Eagles at Highmark Stadium. This prediction is based on the model giving the Bills a 56% chance of winning the game.

Furthermore, Dimers predicts that the bookmakers have gotten it right and the Eagles and Bills each have a 50% chance of covering the spread, while the 43.5-point over/under is also considered an equal 50-50 chance of hitting.

These predictions and probabilities are correct at the time of publication but are subject to potential changes.

Eagles vs. Bills best bet

Our top pick for the Eagles vs. Bills Week 17 NFL matchup is to bet on the Bills moneyline (-110).

This betting advice is based on comprehensive simulations and valuable betting intelligence, designed to assist you in making more informed investments.

Score prediction for Eagles vs. Bills

Dimers’ predicted final score for the Philadelphia vs. Buffalo game on Sunday has the Bills winning 22-21.

This expert prediction is based on each team’s average score following 10,000 game simulations, offering a glimpse into the potential outcome.

NFL player props: Sunday

NFL props are an exciting way to wager on Sunday’s game without necessarily betting on its outcome.

This article features the most likely first and anytime touchdown scorers for the Eagles and Bills, as well as projected player stats.

Philadelphia EaglesFirst touchdown scorer predictionsSaquon Barkley: 10.4% probabilityJalen Hurts: 9.4% probabilityA.J. Brown: 7.2% probabilityAnytime touchdown predictionsSaquon Barkley: 52.1% probabilityJalen Hurts: 48.7% probabilityA.J. Brown: 40.0% probabilityProjected box score leadersQB passing yards: Jalen Hurts, 197 yardsReceiving yards: A.J. Brown, 66 yardsRushing yards: Saquon Barkley, 79 yardsBuffalo BillsFirst touchdown scorer predictionsJames Cook: 11.5% probabilityJosh Allen: 7.8% probabilityKhalil Shakir: 5.6% probabilityAnytime touchdown predictionsJames Cook: 56.6% probabilityJosh Allen: 43.2% probabilityKhalil Shakir: 33.1% probabilityProjected box score leadersQB passing yards: Josh Allen, 207 yardsReceiving yards: Khalil Shakir, 46 yardsRushing yards: James Cook, 93 yardsNFL Week 17: Eagles vs. Bills

Get ready for Sunday’s game between the Eagles and Bills in Week 17 of the National Football League season at Highmark Stadium, which is scheduled to start at 4:25 p.m. EST. We emphasize that all of the NFL best bets and NFL predictions in this preview are based on 10,000 data-driven simulations of the Eagles vs. Bills matchup, and they are correct at the time of publication. They are intended to help you make more informed choices when placing bets at online sportsbooks.

Please note that when engaging in online betting, it is important to exercise responsible gambling practices and seek reputable sources for accurate and up-to-date information.

ABOUT THE AUTHOR

Mac Douglass | Special Correspondent

Mac Douglass is the Senior Sports Betting Editor at Cipher Sports Technology Group. In addition to covering the sports betting industry for several news sites across the US, Mac provides Formula 1 analysis and betting tips for Dimers, and tennis commentary for Stats Insider.

Ryan Leaver | Special Correspondent

Ryan Leaver is a highly experienced sports betting digital content producer for Cipher Sports Technology Group. He boasts an impressive writing portfolio, contributing to prominent platforms like Dimers, Fox Sports, Stats Insider, and Triple M.

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