In what could be a lopsided matchup, the New Orleans Saints (0-3) travel to Orchard Park to play the Buffalo Bills (3-0). Here are the odds, predictions, and free expert picks for Saints vs. Bills.
Best Betting Sites For Saints vs. Bills
- BetUS — 125% Bonus, Up To $2,625 On Your First 3 Deposits
- BetNow — $2,500 NFL Betting Bonus
- BetWhale — 200% Welcome Bonus, Up To $6,000
- BetOnline — $250 In Free NFL Bets
- MyBookie — 100% Deposit Bonus, Up to $500
Saints vs. Bills: Game Information
Home classics.@DeltaSonicWash | #BillsMafia pic.twitter.com/rDdaMYsS1D
— Buffalo Bills (@BuffaloBills) September 23, 2025
- 🏈 Game: Saints vs. Bills
- 🕗 Time: 1 p.m. ET
- 🏟 Location: Highmark Stadium — Orchard Park, New York
- 📺 TV Channel: CBS
- 💻 Live Stream: Paramount+, NFL+
Saints vs. Bills Odds and Predictions
This is where the Saints are these days…
They opened as 15.5-point underdogs to the Bills on Sunday, making them the largest underdogs they've been in an NFL game in 40 years. The Saints were 16-point underdogs to the 49ers in 1985.
— Jeff Duncan (@JeffDuncan_) September 23, 2025
Through three weeks, the New Orleans Saints have already established themselves as one of the five worst teams in the NFL.
After playing two competitive games at home, the Saints were blown out by the Seahawks in Week 3 by a score of 44-13.
Spencer Rattler is now 0-9 as a starter in the NFL. Rattler is in line to start against the Bills.
Meanwhile, Allen and the Bills continue to prove why they’re the top team in the AFC after a 31-21 win over the Dolphins.
Allen’s stats aren’t eye-popping: 755 yards, five passing touchdowns, and two rushing touchdowns.
Allen’s most impressive number is zero, the number of turnovers Allen has through three games. If Allen limits his mistakes, the Bills are almost impossible to beat.
This has a chance to be the largest spread of the season. Most books have it at either 16.5 or 17 in favor of the Bills.
When Allen is a huge favorite, he almost never loses — 27-2 SU when the Bills are an 8.5 favorite or higher. Covering the number is another story. The Bills are 8-10-2 ATS in their last 20 games as double-digit favorites.
If you don’t want to lay the points, take the Bills’ first quarter or first half. If we have to pick a side, we’ll lay the 17 points and hope Buffalo gets off to a fast start.
Pick: Bills -17 (+100)
Saints vs. Bills Prop
Speaking of the first quarter, that’s the prop bet we’re going to take.
Buffalo ranks fourth in the NFL with an average of 8.0 points in the first quarter.
On the other side, the Saints are one of two teams with zero points in the first quarter. The Saints have been outscored 30-0 in the first quarter this year.
The Bills should go right down the field on their opening drive to put points on the board.
