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NFL: Saints vs. Bills, Prediction, Odds, Best Bet

Derek Mountain
Derek Mountain Sports Betting Expert
8 minute read
NFL: Saints vs. Bills, Prediction, Odds, Best Bet

Featured Image Credit: Mark Konezny via Imagn Images

NO @ BUF Odds

  • Full Game
  • 1H
  • 1Q
  • 2Q
  • 3Q
  • 4Q
  • Spread
  • Total
  • Moneyline
Final
New Orleans Saints 255 Saints
+12.5 -110 +9.5 -115 +9.5 -110 +9.5 +105 +8.5 -107 +8.5 -110 +10.5 -145 +7.5 -140 +9.5 -108 +14.5 -105  
Buffalo Bills 256 Bills
-12.5 -110 -9.5 -105 -9.5 -110 -9.5 -125 -8.5 -114 -8.5 -110 -10.5 +120 -7.5 +105 -9.5 -115 -14.5 -115  
Final
New Orleans Saints 255 Saints
o46.5 -110 o24.5 -110 N/A o24.5 -110 o24.5 -114 o24.5 -105 o24.5 -110 o32.5 -125 o24.5 -117 o48.5 -105  
Buffalo Bills 256 Bills
u46.5 -110 u24.5 -110 N/A u24.5 -110 u24.5 -107 u24.5 -115 u24.5 -110 u32.5 -105 u24.5 -108 u48.5 -115  
Final
New Orleans Saints 255 Saints
+470 +390 N/A +500 +380 +430 N/A +375 +500 +750  
Buffalo Bills 256 Bills
-650 -575 N/A -625 -590 -650 N/A -575 -770 -1450  
Final
New Orleans Saints 255 Saints
+12.5 -110 +3.5 -110 +3.5 -110 +3.5 -102 +3.5 -105 +3.5 -112 +3.5 -105 +1.5 -105 +4.5 -127 +14.5 -105  
Buffalo Bills 256 Bills
-12.5 -110 -3.5 -110 -3.5 -110 -3.5 -118 -3.5 -125 -3.5 -108 -3.5 -115 -1.5 -125 -4.5 +102 -14.5 -115  
Final
New Orleans Saints 255 Saints
o46.5 -110 o9.5 -125 N/A o9.5 -122 o9.5 -130 o9.5 -126 o9.5 -125 o18.5 +105 o9.5 -150 o48.5 -105  
Buffalo Bills 256 Bills
u46.5 -110 u9.5 +105 N/A u9.5 even u9.5 even u9.5 +102 u9.5 +105 u18.5 -140 u9.5 +120 u48.5 -115  
Final
New Orleans Saints 255 Saints
+470 +270 N/A +300 +270 +270 N/A +500 +370 +750  
Buffalo Bills 256 Bills
-650 -340 N/A -375 -350 -370 N/A -900 -530 -1450  
Final
New Orleans Saints 255 Saints
+12.5 -110 +6.5 even N/A +5.5 -102 +7.5 -125 +6.5 -100 N/A +5.5 -110 +6.5 -115 +14.5 -105  
Buffalo Bills 256 Bills
-12.5 -110 -6.5 -120 N/A -5.5 -118 -7.5 +105 -6.5 -120 N/A -5.5 -120 -6.5 -108 -14.5 -115  
Final
New Orleans Saints 255 Saints
o46.5 -110 o23.5 -105 N/A o22.5 -115 o22.5 -110 o23.5 -100 o23.5 -110 o22.5 -140 o23.5 -106 o48.5 -105  
Buffalo Bills 256 Bills
u46.5 -110 u23.5 -115 N/A u22.5 -105 u22.5 -110 u23.5 -120 u23.5 -120 u22.5 +105 u23.5 -117 u48.5 -115  
Final
New Orleans Saints 255 Saints
+470 +325 N/A +250 N/A +330 N/A +260 +265 +750  
Buffalo Bills 256 Bills
-650 -425 N/A -310 N/A -440 N/A -375 -360 -1450  
Final
New Orleans Saints 255 Saints
+12.5 -110 N/A N/A +4.5 -120 N/A +5.5 -110 +5.5 -110 +5.5 -135 N/A +14.5 -105  
Buffalo Bills 256 Bills
-12.5 -110 N/A N/A -4.5 even N/A -5.5 -110 -5.5 -120 -5.5 even N/A -14.5 -115  
Final
New Orleans Saints 255 Saints
o46.5 -110 o13.5 -110 N/A o14.5 -108 N/A o10.5 +146 o15.5 -120 o14.5 -105 N/A o48.5 -105  
Buffalo Bills 256 Bills
u46.5 -110 u13.5 -110 N/A u14.5 -112 N/A u10.5 -200 u15.5 -110 u14.5 -125 N/A u48.5 -115  
Final
New Orleans Saints 255 Saints
+470 +320 N/A +275 N/A +310 N/A +260 N/A +750  
Buffalo Bills 256 Bills
-650 -380 N/A -345 N/A -430 N/A -375 N/A -1450  
Final
New Orleans Saints 255 Saints
+12.5 -110 N/A N/A +3.5 -115 N/A +3.5 -110 +3.5 -115 +1.5 -105 N/A +14.5 -105  
Buffalo Bills 256 Bills
-12.5 -110 N/A N/A -3.5 -105 N/A -3.5 -114 -3.5 -115 -1.5 -125 N/A -14.5 -115  
Final
New Orleans Saints 255 Saints
o46.5 -110 o10 even N/A o9.5 -130 N/A o10.5 +106 o9.5 -150 o10.5 +120 N/A o48.5 -105  
Buffalo Bills 256 Bills
u46.5 -110 u10 -120 N/A u9.5 +110 N/A u10.5 -138 u9.5 +115 u10.5 -165 N/A u48.5 -115  
Final
New Orleans Saints 255 Saints
+470 +225 N/A +240 N/A +270 N/A +175 N/A +750  
Buffalo Bills 256 Bills
-650 -275 N/A -298 N/A -375 N/A -240 N/A -1450  
Final
New Orleans Saints 255 Saints
+12.5 -110 +3 -110 N/A +3.5 -125 N/A +2.5 +108 +3.5 -110 +3.5 -120 N/A +14.5 -105  
Buffalo Bills 256 Bills
-12.5 -110 -3 -110 N/A -3.5 +105 N/A -2.5 -130 -3.5 -120 -3.5 -110 N/A -14.5 -115  
Final
New Orleans Saints 255 Saints
o46.5 -110 o13.5 -110 N/A o13.5 +105 N/A o12.5 -122 o13.5 even o12.5 -140 N/A o48.5 -105  
Buffalo Bills 256 Bills
u46.5 -110 u13.5 -110 N/A u13.5 -125 N/A u12.5 -100 u13.5 -130 u12.5 +105 N/A u48.5 -115  
Final
New Orleans Saints 255 Saints
+470 +180 N/A +210 N/A +198 N/A +200 N/A +750  
Buffalo Bills 256 Bills
-650 -225 N/A -258 N/A -250 N/A -275 N/A -1450  

The Saints will take on the Bills in this week's NFL action. Kickoff is set for 1:00 p.m. EDT at Highmark Stadium in Orchard Park, N.Y. The game will be broadcast live on CBS. Here's everything you need to know about Saints vs. Bills odds, the latest NFL spreads, NFL over/unders and more.

The Bills opened as a -16 point favorite over Saints. The total is set at over/under 48.5 total points scored by both teams combined.

Be sure to check out the latest NFL odds and stay up to date on the latest sportsbook promos, including the bet365 bonus code!

Updated on 1/28/26

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New Orleans Saints vs. Buffalo Bills Best Bet

New Orleans has the 5th worst pressure rate vs. expected so far in 2025 and 5th worst raw pressure rate.

Josh Allen's scramble rate has decreased by more than 10% with a clean pocket than facing pressure since the start of last year The Saints also play zone at a top-six rate in the NFL, including Cover 3 at the third-highest rate which is the hardest to scramble against with an extra man in the box and zone coverage with the DBs facing the QB.

As huge favorites, Allen likely won’t be asked to do much on designed runs with his legs.

There's the chance he might get a couple kneel downs, but with a strong chance of a blowout, it would be backup Mitch Trubisky taking the knees in that scenario.

Since start of last year: Trubisky has taken all the 2H kneels in double-digit BUF wins Allen has taken all the 2H knees in single-digit BUF wins.

Saints vs. Bills Best Bet: Josh Allen Under 6.5 Rushing Attempts

(Pick from Nick Giffen)

Looking for more best bets? Check out our free NFL picks and our premium subscription for the best picks!

What Time is the New Orleans Saints vs. Buffalo Bills Game?

The New Orleans Saints vs. Buffalo Bills at 1:00 PM ET on Sunday, September 28th.

Where is the New Orleans Saints vs. Buffalo Bills Being Played?

This game will be played at Highmark Stadium in Orchard Park, New York.

How Can I Watch Commanders vs. Falcons?

You can watch Saints vs. Bills on CBS.

Can the Saints Beat the Bills?

It would take a minor miracle as a Saints win would be the biggest upset of the NFL season.

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Derek Mountain

Derek Mountain

Derek Mountain works in the Boston area as an SEO Performance Associate for Better Collective. Derek is a recent graduate of the College of the Holy Cross in Worcester, MA where he played football for five years as well as walking on the basketball team his freshman year. Derek has experience writing and editing casino content for nearly four years. More from Derek Mountain
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