Sign Up Subscribe
Featured Last Updated Sep 25 2025, 2:23 PM

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
New Orleans Saints 255 Saints
+12.5 -110 +9.5 -105 + +9.5 -102 + +9.5 -108 + +9.5 -109 + +9.5 -115 + +9.5 -110 + +9.5 -105 +7.5 -109 + +9.5 -110 +15.5 -112  
Buffalo Bills 256 Bills
-12.5 -110 -9.5 -115 + -9.5 -118 + -9.5 -112 + -9.5 -112 + -9.5 -115 + -9.5 -110 + -9.5 -115 -7.5 -114 + -9.5 -110 -15.5 -108  
New Orleans Saints 255 Saints
o46.5 -110 o24.5 -105 + N/A o24.5 -105 + o24.5 -110 + N/A o24.5 -105 + o24.5 -105 o24.5 -106 + o24.5 -105 o47.5 -115  
Buffalo Bills 256 Bills
u46.5 -110 u24.5 -115 + N/A u24.5 -115 + u24.5 -110 + N/A u24.5 -115 + u24.5 -115 u24.5 -118 + u24.5 -115 u47.5 -105  
New Orleans Saints 255 Saints
+470 +475 + N/A +455 + +450 + +450 + +450 + +450 +420 + N/A +850  
Buffalo Bills 256 Bills
-650 -650 + N/A -625 + -750 + -900 + -650 + -630 -625 + N/A -1450  
New Orleans Saints 255 Saints
+12.5 -110 +3.5 -110 + +3.5 -105 + +3.5 +102 + +3.5 -105 + N/A +3.5 -108 + +3.5 -110 +3.5 -118 + +3.5 even +15.5 -112  
Buffalo Bills 256 Bills
-12.5 -110 -3.5 -110 + -3.5 -118 + -3.5 -125 + -3.5 -125 + N/A -3.5 -114 + -3.5 -120 -3.5 -105 + -3.5 -120 -15.5 -108  
New Orleans Saints 255 Saints
o46.5 -110 o9.5 -130 + N/A o9.5 -142 + o9.5 -130 + N/A o9.5 -126 + o8.5 -165 o9.5 -136 + o9.5 -125 o47.5 -115  
Buffalo Bills 256 Bills
u46.5 -110 u9.5 +110 + N/A u9.5 +120 + u9.5 even + N/A u9.5 +104 + u8.5 +120 u9.5 +108 + u9.5 +105 u47.5 -105  
New Orleans Saints 255 Saints
+470 +275 + N/A +295 + +270 + N/A +280 + +280 +255 + N/A +850  
Buffalo Bills 256 Bills
-650 -350 + N/A -375 + -350 + N/A -370 + -400 -345 + N/A -1450  
New Orleans Saints 255 Saints
+12.5 -110 +7 -105 + N/A +6.5 -105 + +7.5 -125 + N/A +6.5 +105 + N/A +7.5 -122 + N/A +15.5 -112  
Buffalo Bills 256 Bills
-12.5 -110 -7 -115 + N/A -6.5 -115 + -7.5 +105 + N/A -6.5 -125 + N/A -7.5 -103 + N/A -15.5 -108  
New Orleans Saints 255 Saints
o46.5 -110 o21.5 -120 + N/A o23.5 even + o22.5 -110 + N/A o22.5 -120 + N/A o23.5 -108 + o22.5 -120 o47.5 -115  
Buffalo Bills 256 Bills
u46.5 -110 u21.5 even + N/A u23.5 -120 + u22.5 -110 + N/A u22.5 -100 + N/A u23.5 -115 + u22.5 -110 u47.5 -105  
New Orleans Saints 255 Saints
+470 +320 + N/A +310 + N/A N/A +350 + N/A +350 + N/A +850  
Buffalo Bills 256 Bills
-650 -400 + N/A -395 + N/A N/A -440 + N/A -500 + N/A -1450  
New Orleans Saints 255 Saints
+12.5 -110 N/A N/A +5.5 -112 + N/A N/A +5.5 -108 + N/A N/A +4.5 -115 +15.5 -112  
Buffalo Bills 256 Bills
-12.5 -110 N/A N/A -5.5 -108 + N/A N/A -5.5 -114 + N/A N/A -4.5 -115 -15.5 -108  
New Orleans Saints 255 Saints
o46.5 -110 o13.5 -110 + N/A o14.5 +102 + N/A N/A o14.5 -110 + N/A N/A o15.5 -115 o47.5 -115  
Buffalo Bills 256 Bills
u46.5 -110 u13.5 -110 + N/A u14.5 -122 + N/A N/A u14.5 -110 + N/A N/A u15.5 -115 u47.5 -105  
New Orleans Saints 255 Saints
+470 +325 + N/A +300 + N/A N/A +320 + N/A N/A N/A +850  
Buffalo Bills 256 Bills
-650 -425 + N/A -410 + N/A N/A -430 + N/A N/A N/A -1450  
New Orleans Saints 255 Saints
+12.5 -110 N/A N/A +3.5 -115 + N/A N/A +3.5 -104 + N/A N/A +3.5 -115 +15.5 -112  
Buffalo Bills 256 Bills
-12.5 -110 N/A N/A -3.5 -105 + N/A N/A -3.5 -118 + N/A N/A -3.5 -115 -15.5 -108  
New Orleans Saints 255 Saints
o46.5 -110 o10 -110 + N/A o9.5 -130 + N/A N/A o9.5 -144 + N/A N/A o9.5 -140 o47.5 -115  
Buffalo Bills 256 Bills
u46.5 -110 u10 -110 + N/A u9.5 +110 + N/A N/A u9.5 +118 + N/A N/A u9.5 +110 u47.5 -105  
New Orleans Saints 255 Saints
+470 +230 + N/A +250 + N/A N/A +285 + N/A N/A N/A +850  
Buffalo Bills 256 Bills
-650 -280 + N/A -310 + N/A N/A -375 + N/A N/A N/A -1450  
New Orleans Saints 255 Saints
+12.5 -110 +3 -110 + N/A +3.5 -130 + N/A N/A +3.5 -130 + N/A N/A +3.5 -105 +15.5 -112  
Buffalo Bills 256 Bills
-12.5 -110 -3 -110 + N/A -3.5 +110 + N/A N/A -3.5 +108 + N/A N/A -3.5 -125 -15.5 -108  
New Orleans Saints 255 Saints
o46.5 -110 o13.5 -110 + N/A o13.5 +102 + N/A N/A o12.5 -118 + N/A N/A o12.5 -120 o47.5 -115  
Buffalo Bills 256 Bills
u46.5 -110 u13.5 -110 + N/A u13.5 -122 + N/A N/A u12.5 -104 + N/A N/A u12.5 -110 u47.5 -105  
New Orleans Saints 255 Saints
+470 +185 + N/A +210 + N/A N/A +210 + N/A N/A N/A +850  
Buffalo Bills 256 Bills
-650 -225 + N/A -258 + N/A N/A -265 + N/A N/A 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 9/25/25

bet365
Bet $5, Get $200 in Bonus Bets Win or Lose!
Bonus Code
VIBONUS
Claim $200
New customers only, 21+ (18+ in KY). Gambling Problem? Call 1-800-GAMBLER. Available in AZ, CO, IA, IL, IN, KS, KY, LA, MD, NC, NJ, OH, PA, TN, VA only. Bet $5 and Get $200 in Bonus Bets at bet365. Registration required. Minimum $10 deposit required. Minimum odds -500 of greater. Bonus Bets wager excluded from returns. T&Cs, time limits and exclusions apply.

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.

Featured News

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
•