Saints vs. Bills prediction: Buffalo favored to win in NFL Week 4, 2025

The Buffalo Bills will face the New Orleans Saints in NFL Week 4 action at Highmark Stadium on Sunday, beginning at 1:00PM ET.

Based on updated simulation results, Dimers' proven NFL model projects the Bills as the most likely winner of today's game.

"Using the most recent data, our experts ran 10,000 simulations of Sunday's Saints-Bills game," said Dimers' Chief Content Officer, Nick Slade.

"After accounting for recent updates and other variables, our prediction shows the Bills with a win probability of 89%, while the Saints have 11%."

This gameday Saints vs. Bills betting preview builds on my Saints vs. Bills prediction that was published earlier in the week.

For expanded analysis of today’s game, including the predicted score, best bets and player prop picks, visit our interactive Saints vs. Bills predictions page.

Saints vs. Bills Predictions

Since our Saints-Bills predictions earlier in the week, we have simulated the outcome of Sunday's NFL matchup between the Saints and Bills 10,000 times as part of our NFL predictions coverage.

Our leading predictive model gives the Bills an 89% chance of beating the Saints in Week 4 of the NFL season. Our predicted final score has the Bills winning 31-17.

According to our model, the Saints (+15.5) have a 56% chance of covering the spread, while the 48.5-point over/under has an equal 50-50 chance of hitting.

Saints vs. Bills odds

We have sourced the best NFL odds in America for this game, which are listed here:

Bet Type	Saints	Bills
Spread	+15.5 (-115)	-15.5 (-105)
Moneyline	+900	-1350
Total	o48.5 (-105)	u48.5 (-110)

All odds are correct at the time of publication and are subject to change.

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Saints vs. Bills picks and best bets

Our model's strongest edge in today's Saints vs. Bills matchup is on the total.

Our expert predictions, aligned with the best odds, reveal the best NFL picks and NFL best bets for every game throughout the season.

Unlimited access to our full set of picks, including this one, is available via Dimers Pro.

Saints vs. Bills TD scorers

Who will score the first touchdown in Saints vs. Bills?

According to our model, Buffalo's James Cook is most likely to score the first touchdown in Saints vs. Bills.

Our projections give Cook a 14.9% chance of scoring the first TD at Highmark Stadium, while the Bills running back is a 59.3% chance of scoring an anytime touchdown.

First touchdown scorer predictions

New Orleans Saints

Player	First TD Probability
Alvin Kamara (RB)	9.6%
Juwan Johnson (TE)	5.4%
Chris Olave (WR)	5.1%

Buffalo Bills

Player	First TD Probability
James Cook (RB)	14.9%
Josh Allen (QB)	11.7%
Keon Coleman (WR)	5.9%

Anytime touchdown scorer predictions

New Orleans Saints

Player	Anytime TD Probability
Alvin Kamara (RB)	39.3%
Juwan Johnson (TE)	24.3%
Chris Olave (WR)	23.3%

Buffalo Bills

Player	Anytime TD Probability
James Cook (RB)	59.3%
Josh Allen (QB)	50.8%
Keon Coleman (WR)	29.9%

Saints vs Bills player props

Discover our predictions for the players likely to lead in passing, rushing and receiving yards for both the Saints and Bills. For detailed projections, join Dimers Pro.

Already a Dimers Pro member? Head to our Saints-Bills page now to access every player prop projection.

Saints vs. Bills quarterbacks

Of the starting quarterbacks, the Saints' Spencer Rattler is projected to throw for fewer yards than the Bills' Josh Allen.

Saints rushing

Alvin Kamara, Spencer Rattler and Kendre Miller are projected to be the leading rushers for the Saints.

Player	Position
Alvin Kamara	RB
Spencer Rattler	QB
Kendre Miller	RB

Bills rushing

James Cook, Josh Allen and Ray Davis are expected to lead the Bills in rushing yards.

Player	Position
James Cook	RB
Josh Allen	QB
Ray Davis	RB

Saints receiving

Chris Olave, Juwan Johnson, Rashid Shaheed, Alvin Kamara and Brandin Cooks are projected to top the receiving yards for the Saints.

Player	Position
Chris Olave	WR
Juwan Johnson	TE
Rashid Shaheed	WR
Alvin Kamara	RB
Brandin Cooks	WR

Bills receiving

Keon Coleman, Khalil Shakir, Dalton Kincaid, Joshua Palmer and James Cook are projected to lead the Bills in receiving yards.

Player	Position
Keon Coleman	WR
Khalil Shakir	WR
Dalton Kincaid	TE
Joshua Palmer	WR
James Cook	RB

Saints vs. Bills game-day updates and essential details

The NFL Week 4 action between the Bills and Saints at Highmark Stadium is scheduled to start at 1:00PM ET.

• Who: New Orleans Saints vs. Buffalo Bills
• Date: Sunday, September 28, 2025
• Time: 1:00PM ET/10:00AM PT
• Venue: Highmark Stadium

Dimers' comprehensive preview of Sunday's Saints vs. Bills matchup includes our prediction, picks and the latest betting odds.

Before making any Saints vs. Bills picks, be sure to check out the latest NFL predictions and betting advice from Dimers Pro.

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Conclusion

We predict the Bills, with an 89% win probability, will likely beat the Saints in Week 4 of the NFL season.

AI and automation have enhanced this article to quickly deliver accurate Saints vs. Bills insights, with human oversight ensuring high editorial quality. Our predictions are drawn from up-to-date data to help you make informed decisions. For additional resources and advice on responsible gambling, please call 1-800-GAMBLER.

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