Buffalo Bills running back James Cook (4) in action against the New Orleans Saints at Highmark Stadium in Orchard Park, New York.

The New England Patriots (2-2) take on the Buffalo Bills (4-0) in a AFC East rivalry matchup in Orchard Park, New York, on Sunday Night Football. Kickoff from Highmark Stadium is set for 8:20 p.m. ET (NBC/Peacock). Let's analyze BetMGM Sportsbook's NFL odds around the Patriots vs. Bills odds and make our expert NFL picks and predictions for the best bets.

New England destroyed the Carolina Panthers 42-13 in Week 4 while covering as a 5.5-point favorite as the Over (41.5) cashed. The Pats gave up the first score in that outing before proceeding to force either a punt, turnover, or missed field goal for all of Carolina's next 9 drives. The Patriots also picked up 2 much-needed special teams TDs in the win, including a first-quarter 87-yard punt return by CB Marcus Jones.

Buffalo picked up a 31-19 win over the New Orleans Saints last week while failing to cover as a 14.5-point favorite as the Over (49) hit. RB James Cook had 117 rushing yards and a TD, averaging 5.3 yards per carry, while the Bills rushed for 165 yards and 2 TDs as a team. The Bills have put up at least 30 points in all of their 4 games.

These squads last faced off in Week 18 last season, when the Patriots came away with a 23-16 home win in which both teams sat many of their key starters. Buffalo is 7-3 in the last 10 matchups.

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Patriots at Bills odds

Provided by BetMGM Sportsbook; access USA TODAY Sports Scores and Sports Betting Odds hub for a full list. Lines last updated at 11:13 a.m. ET.

  • Moneyline (ML): Patriots +350 (bet $100 to win $350) | Bills -450 (bet $450 to win $100)
  • Against the spread (ATS): Patriots +8 (-110) | Bills -8 (-110)
  • Over/Under (O/U): 49.5 (O: -110 | U: -110)

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Patriots at Bills key injuries

Patriots

  • LB K'Lavon Chaisson (knee) questionable
  • CB Carlton Davis III (illness) questionable
  • DE Milton Williams (ankle) questionable
  • LB Jahlani Tavai (calf) questionable

Bills

  • OT Spencer Brown (calf) questionable
  • LB Matt Milano (pectoral) questionable
  • DT Ed Oliver (ankle) questionable
  • DT T.J. Sanders (knee) questionable
  • CB Dorian Strong (neck) out
  • LB Dorian Williams (knee) out

Patriots at Bills picks and predictions

Prediction

Bills 21, Patriots 17

Moneyline

PASS.

New England is a solid team that will give Buffalo fits at times, but the Bills are simply too dominant offensively to give away this game. Eventually, they will find success somewhere against this Patriots defense.

The Bills will cover here as -450 favorites, but they are not worth the risk of betting on as such heavy favorites in this divisional matchup. Pass here and bet on the much safer spread.

  • BILLS AT PATRIOTS: Best prop bets

Against the spread

BET PATRIOTS +8 (-110).

New England's passing defense hasn't been great, allowing 241.5 passing yards per game, good for bottom 7 in the NFL. However, with Buffalo not having a clear number 1 pass catcher for QB Josh Allen to rely on, New England CB Christian Gonzalez will have no problem shutting down his entire half of the field. Given that, Allen and this Buffalo offense that has been stellar will struggle to find opportunities to pull away in this one.

Finally, the Patriots have covered the spread in their last 4 matchups with the Bills.

Over/Under

LEAN UNDER 49.5 (-110).

Buffalo loves to open the game up with its running game, but when going against this Pats defense that allows just 77.5 rushing yards per game, the Bills will find that early scores will be hard to come by. On the other side, the Bills are a bottom-2 run defense in the NFL, allowing 164.3 rushing yards per game. This flaw will allow for New England to find enough success offensively to tire out this Buffalo defense and keep Allen off the field.

Buffalo's offense has been explosive to start the season, but this seems like the perfect time for Buffalo's first defensive-oriented game.

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This article originally appeared on Sportsbook Wire: New England Patriots at Buffalo Bills odds, picks and predictions

Reporting by Payton Shanks, Sportsbook Wire / Sportsbook Wire

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