Saints vs Bills Prediction, Picks & Odds | 28 Sep 2025

NFL Betting Preview: Saints vs Bills

The New Orleans Saints lock horns with the Buffalo Bills in this NFL Week 4 matchup at Highmark Stadium, with kickoff scheduled for 13:00 on Sunday, September 28. Our betting preview features expert predictions, picks, updated betting odds, head-to-head stats and the latest team news, including injuries.

The Saints look capable of avoiding a heavy defeat against the Bills and we’re happy to bet them against the spread. The underdogs can comfortably cover +15.5 and this can be backed at -110.

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New Orleans Saints have suffered a defeat in their previous three games including a recent 44-13 loss. This occurred on the road at Lumen Field against Seattle Seahawks. The Saints recorded 284 total yards, made up of 205 through the air and 79 on the ground. The offense scored one touchdown and picked up 21 first downs.

Buffalo Bills were winners for the third straight time in their last game. Landing a 31-21 home victory against Miami Dolphins at Highmark Stadium. The Bills finished with 360 yards, including 203 passing and 157 rushing yards. They picked up 23 first downs and produced 4 TD's, including 3 passing scores and a rushing touchdown.

Head-to-Head Statistics

The Bills triumphed 31-6 when they last played the Saints. This head-to-head was played at Caesars Superdome.

Quarterbacks

Spencer Rattler

203.5 Passing Yards

Over -112

Under -112

Josh Allen

220.5 Passing Yards

Over -112

Under -112

Saints vs Bills Prediction & Picks

We’ve broken down Saints vs Bills from every angle, offering our expert match prediction, expected final score, best player prop recommendations and a well-constructed bet builder.

Game Prediction

The betting line of +15.5 looks too big. We’re very keen to snap up the -110 that the Saints cover an appealing spread in this NFL battle.

Team news and current form always play a key role in shaping our expert NFL picks. We also dig into the latest stats and trends to help deliver the most accurate predictions possible.

Key Saints vs Bills stats:

• The +15.5 line has been covered by Saints in 17 of their last 20 games on the road.
• The +15.5 line has been covered by Saints in 8 of their last 10 games.
• The -15.5 line hasn’t been covered by Bills in 4 of their last 5 games.
• The -15.5 line hasn’t been covered by Bills in 7 of their last 10 games.
• The -15.5 line hasn’t been covered by Bills in 3 consecutive games at home.

Saints +15.5 Probability

The top NFL sportsbooks are estimating that there is a 52.4% chance of this pick winning. However, our analysts in-depth research has found that the actual probability is between 55-60%. It's therefore regarded as a value wager.

The Winning Margin lines allow you to bet on the Saints to claim a victory by a certain number of points. It’s a different wager and a viable alternative to the spread.

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Our Game Prediction

Saints +15.5 @ -110 Bet Now

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Disclosure: This preview contains affiliate links; we may earn a commission at no extra cost to you. T&Cs apply. We only recommend licensed and regulated operators. See our Editorial Policy. Pick odds and lines reflect the price available at the time of publication (19:26, 26 September 2025). Live market odds are updated regularly and may differ. 18+ (or legal age) | Gamble Responsibly.

Player Prop Picks

Top Pick: Alvin Kamara Anytime TD +130

The odds for Alvin Kamara (Saints) to make it to the end zone are +130. He looks like a value bet to punch it in and we recommend backing this Anytime Touchdown Scorer pick.

Latest Alvin Kamara Player Prop Odds

Touchdown

Anytime

+130

First

+900

Receiving Yards

Over 19.5

-112

Under 19.5

-112

Rushing Yards

Over 51.5

-112

Under 51.5

-112

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Spencer Rattler Over 200.5 Passing Yards -114

You can back Spencer Rattler (Saints) at -114 to record more than 200.5 passing yards. The line for him on the Overs looks attractive and bettors can get plenty of juice from this QB Passing Yards wager.

Latest Spencer Rattler Player Prop Odds

Touchdown

Anytime

+700

First

+4000

Passing Yards

Over 203.5

-112

Under 203.5

-112

Rushing Yards

Over 16.5

-112

Under 16.5

-112

Pick odds and lines correct at publication. Live market odds are updated regularly and may differ. T&Cs apply. 18+ (or legal age) | Gamble Responsibly.

Correct Score Prediction

Saints 14 - 27 Bills

Should you want to go for a selection at huge odds, head to the correct score lines where the Bills can be backed speculatively to achieve a 27-14 victory.

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Saints vs Bills Odds

The odds and lines below are updated regularly and may differ from the prices shown in our picks, which are captured at the time of publication.

Buffalo Bills have short betting odds and they’re overwhelming -1429 favorites for this game. This means the sportsbooks give them a 93% chance of winning. At +830, New Orleans Saints are regarded as having a lower probability of winning.

The current spread is 14.5 and the total points line is 48.5. There is no denying the popularity of betting on the Totals. Those who wager Under 48.5 can get -118.

There are a wide range of game lines and team props when it comes to the National Football League and we recommend heading to the top betting apps to find the bet that matches your view on the matchup.

Moneyline

Saints

+830

Bills

-1429

Point Spread

Saints +14.5

-110

Bills -14.5

-110

Total Points

Under 48.5

-118

Over 48.5

-104

Favorite James Cook is now available at +350 to be the First Touchdown Scorer. You will find similar odds apply when it comes to him scoring the last TD.

Touchdown

James Cook (Bills)

First TD

+350

Anytime TD

-185

Josh Allen (Bills)

First TD

+480

Anytime TD

-154

Alvin Kamara (Saints)

First TD

+900

Anytime TD

+130

Keon Coleman (Bills)

First TD

+1000

Anytime TD

+210

Khalil Shakir (Bills)

First TD

+1000

Anytime TD

+210

Dalton Kincaid (Bills)

First TD

+1100

Anytime TD

+220

Joshua Palmer (Bills)

First TD

+1400

Anytime TD

+300

Chris Olave (Saints)

First TD

+1700

Anytime TD

+260

Juwan Johnson (Saints)

First TD

+2000

Anytime TD

+310

Rashid Shaheed (Saints)

First TD

+2200

Anytime TD

+330

Dawson Knox (Bills)

First TD

+2700

Anytime TD

+650

Ray Davis (Bills)

First TD

+3000

Anytime TD

+390

Kendre Miller (Saints)

First TD

+3500

Anytime TD

+650

Spencer Rattler (Saints)

First TD

+4000

Anytime TD

+700

Elijah Moore (Bills)

First TD

+4000

Anytime TD

+750

Brandin Cooks (Saints)

First TD

+5000

Anytime TD

+950

Jackson Hawes (Bills)

First TD

+5000

Anytime TD

+1000

Ty Johnson (Bills)

First TD

+5500

Anytime TD

+500

Tyrell Shavers (Bills)

First TD

+6500

Anytime TD

+1300

Curtis Samuel (Bills)

First TD

+6500

Anytime TD

+1300

Devaughn Vele (Saints)

First TD

+10000

Anytime TD

+1600

Jack Stoll (Saints)

First TD

+10000

Anytime TD

+2000

Kevin Austin (Saints)

First TD

+10000

Anytime TD

+2200

Mason Tipton (Saints)

First TD

+10000

Anytime TD

+3000

Reggie Gilliam (Bills)

First TD

+10000

Anytime TD

+5000

Devin Neal (Saints)

First TD

+10000

Anytime TD

+4500

Velus Jones Jr. (Saints)

First TD

+10000

Anytime TD

+4500

Trey Palmer (Saints)

First TD

+10000

Anytime TD

+1600

Moliki Matavao (Saints)

First TD

+10000

Anytime TD

+4500

Receiving Yards

Chris Olave (Saints)

Over 59.5

-112

Under 59.5

-112

Juwan Johnson (Saints)

Over 42.5

-112

Under 42.5

-112

Khalil Shakir (Bills)

Over 39.5

-112

Under 39.5

-112

Rashid Shaheed (Saints)

Over 38.5

-112

Under 38.5

-112

Keon Coleman (Bills)

Over 37.5

-112

Under 37.5

-112

Dalton Kincaid (Bills)

Over 35.5

-112

Under 35.5

-112

Joshua Palmer (Bills)

Over 23.5

-112

Under 23.5

-112

Alvin Kamara (Saints)

Over 19.5

-112

Under 19.5

-112

Brandin Cooks (Saints)

Over 16.5

-112

Under 16.5

-112

James Cook (Bills)

Over 13.5

-112

Under 13.5

-112

Dawson Knox (Bills)

Over 11.5

-112

Under 11.5

-112

Rushing Yards

James Cook (Bills)

Over 78.5

-112

Under 78.5

-112

Alvin Kamara (Saints)

Over 51.5

-112

Under 51.5

-112

Josh Allen (Bills)

Over 26.5

-112

Under 26.5

-112

Ray Davis (Bills)

Over 18.5

-112

Under 18.5

-112

Spencer Rattler (Saints)

Over 16.5

-112

Under 16.5

-112

Kendre Miller (Saints)

Over 14.5

-112

Under 14.5

-112

Passing Yards

Josh Allen (Bills)

Over 220.5

-112

Under 220.5

-112

Spencer Rattler (Saints)

Over 203.5

-112

Under 203.5

-112

An increasing number of bettors are now enjoying micro betting on the NFL and it’s something which is available on an in-game basis. Wait for the action to start and then wager on something specific to happen.

Can Bills Make It Another Home Victory?

The Bills own a 10-0 mark in their past 10 home games, scoring 32.30 points per contest and conceding 19.60.

The Saints are on a skid of three straight road defeats. They have three wins and seven losses in the last 10 games on the road, scoring 18.00 points per contest and conceding 24.90.

Last 10 Games		W-L	P	PF	PA	O48.5	U48.5
Bills Home Stats		10-0	51.90	32.30	19.60	6	4
Saints Away Stats		3-7	42.90	18.00	24.90	3	7

• W-L = Wins-Losses
• P = Avg. Points
• PF = Avg. Points For
• PA = Avg. Points Against
• O48.5 = Games Over 48.5 Points
• U48.5 = Games Under 48.5 Points

Latest regular season and playoff games stats.

New Orleans Saints Stats

Buffalo Bills Stats

Moneyline

• 2 wins and 8 defeats in the last 10 games
• 3 wins and 7 defeats in the last 10 games on the road

Moneyline

• 8 wins and 2 defeats in the last 10 games
• 10 wins and 0 defeats in the last 10 home games

Point Spread

• +15.5 Betting Line: Have covered the spread in 8 of the last 10 games
• +15.5 Betting Line on the Road: Have covered the spread in 7 of the last 10 games on the road

Point Spread

• -15.5 Betting Line: Have covered the spread in 3 of the last 10 games
• -15.5 Betting Line at Home: Have covered the spread in 4 of the last 10 home games

Total Points

• Game Totals: An average of 40.00 pts in the previous 10 games
• Game Totals on the Road: An average of 42.90 pts in the previous 10 games on the road
• Over 48.5: Covered in 2 of the previous 10 games
• Over 48.5 on the Road: Covered in 3 of the previous 10 games on the road
• Team Totals: Have scored an average of 15.80 pts and allowed 24.20 pts in the last 10 games
• Team Totals on the Road: Have scored an average of 18.00 pts and allowed 24.90 pts in the last 10 games on the road

Total Points

• Game Totals: An average of 55.20 pts in the previous 10 games
• Game Totals at Home: An average of 51.90 pts in the previous 10 home games
• Over 48.5: Covered in 6 of the previous 10 games
• Over 48.5 at Home: Covered in 6 of the previous 10 home games
• Team Totals: Have scored an average of 31.70 pts and allowed 23.50 pts in the last 10 games
• Team Totals at Home: Have scored an average of 32.30 pts and allowed 19.60 pts in the last 10 home games

Game Stats

Last 10 Games

• Total Yards: Gained 299.40 Yds. Allowed 354.30 Yds
• Rushing Yards: Gained 103.80 Yds. Allowed 130.40 Yds
• Passing Yards: Gained 195.60 Yds. Allowed 223.90 Yds
• Total Touchdowns: Scored 1.70 TD. Allowed 2.70 TD
• Rushing Touchdowns: Scored 0.50 TD. Allowed 0.80 TD
• Passing Touchdowns: Scored 1.20 TD. Allowed 1.80 TD
• Total 1st Downs: Picked up 18.20. Allowed 21.30
• Total Turnovers: Committed 1.00. Committed by opponents 0.40
• Total Penalties: Committed 7.50. Committed by opponents 7.00
• Penalty Yards: Lost 56.80 Yds. Gained 57.40 Yds

Game Stats

Last 10 Games

• Total Yards: Gained 386.80 Yds. Allowed 336.10 Yds
• Rushing Yards: Gained 158.90 Yds. Allowed 122.10 Yds
• Passing Yards: Gained 227.90 Yds. Allowed 214.00 Yds
• Total Touchdowns: Scored 3.80 TD. Allowed 3.00 TD
• Rushing Touchdowns: Scored 2.10 TD. Allowed 1.10 TD
• Passing Touchdowns: Scored 1.60 TD. Allowed 1.90 TD
• Total 1st Downs: Picked up 23.10. Allowed 21.00
• Total Turnovers: Committed 0.10. Committed by opponents 1.50
• Total Penalties: Committed 6.00. Committed by opponents 6.40
• Penalty Yards: Lost 46.70 Yds. Gained 48.80 Yds

Last 10 Games on the Road

• Total Yards: Gained 318.50 Yds. Allowed 354.50 Yds
• Rushing Yards: Gained 109.10 Yds. Allowed 112.00 Yds
• Passing Yards: Gained 209.40 Yds. Allowed 242.50 Yds
• Total Touchdowns: Scored 2.00 TD. Allowed 2.60 TD
• Rushing Touchdowns: Scored 0.90 TD. Allowed 1.20 TD
• Passing Touchdowns: Scored 1.00 TD. Allowed 1.10 TD
• Total 1st Downs: Picked up 19.50. Allowed 19.10
• Total Turnovers: Committed 0.80. Committed by opponents 1.20
• Total Penalties: Committed 7.00. Committed by opponents 7.20
• Penalty Yards: Lost 61.00 Yds. Gained 61.60 Yds

Last 10 Home Games

• Total Yards: Gained 372.50 Yds. Allowed 316.30 Yds
• Rushing Yards: Gained 138.30 Yds. Allowed 132.40 Yds
• Passing Yards: Gained 234.20 Yds. Allowed 183.90 Yds
• Total Touchdowns: Scored 3.90 TD. Allowed 2.50 TD
• Rushing Touchdowns: Scored 1.90 TD. Allowed 0.80 TD
• Passing Touchdowns: Scored 1.90 TD. Allowed 1.70 TD
• Total 1st Downs: Picked up 22.60. Allowed 20.00
• Total Turnovers: Committed 0.30. Committed by opponents 1.90
• Total Penalties: Committed 5.30. Committed by opponents 6.60
• Penalty Yards: Lost 40.50 Yds. Gained 50.80 Yds

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