New Orleans Saints vs Buffalo Bills Prediction & Picks - NFL

USA - NFL

New Orleans Saints
9/28/25 13:00
Buffalo Bills

Prediction:

 

James Cook Anytime Touchdown

-175
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 by Matt Lowrimore in NFL Picks

One of the games on the Week 4 Sunday NFL slate will feature a matchup between the Buffalo Bills and the New Orleans Saints. Let’s take a look at the match statistics and predictions for this game between the Bills and the Saints.

New Orleans enters this game with a record of 0-3, having most recently lost to the Seattle Seahawks in Week 3 by a score of 44-13. The Saints’ offense had a total of 284 yards, while its defense allowed 320 yards. Quarterback Spencer Rattler threw for 218 yards, one touchdown, and one interception, while running back Alvin Kamara led the team in rushing with 42 yards.

As for Buffalo, they enter this game with a record of 3-0, having most recently beaten the Miami Dolphins in Week 3 by a score of 31-21. The Bills’ offense had a total of 360 yards, while its defense allowed 276 yards. Quarterback Josh Allen threw for 213 yards and three touchdowns, while running back James Cook led the team in rushing with 108 yards and one touchdown.

New Orleans Saints vs Buffalo Bills Form

Table

Teams % P W D L
5
Buffalo Bills
Buffalo Bills
1 3 3 0 0
31
New Orleans Saints
New Orleans Saints
0 3 0 0 3

New Orleans Saints and Buffalo Bills Latest Matches

New Orleans Saints
New Orleans Saints Latest matches
L L L L L L
Victories

0/6 (0%)

Draw

0/6 (0%)

Defeats

6/6 (100%)

Sep 21, 2025 - NFL

New Orleans Saints
13 :  44
Seattle Seahawks

Sep 14, 2025 - NFL

San Francisco 49ers
26 :  21
New Orleans Saints

Sep 7, 2025 - NFL

Arizona Cardinals
20 :  13
New Orleans Saints

Jan 5, 2025 - NFL

New Orleans Saints
19 :  27
Tampa Bay Buccaneers

Dec 29, 2024 - NFL

Las Vegas Raiders
25 :  10
New Orleans Saints

Dec 23, 2024 - NFL

New Orleans Saints
0 :  34
Green Bay Packers
W L L L L L
Victories

1/6 (17%)

Draw

0/6 (0%)

Defeats

5/6 (83%)

Sep 14, 2025 - NFL

San Francisco 49ers
26 :  21
New Orleans Saints

Sep 7, 2025 - NFL

Arizona Cardinals
20 :  13
New Orleans Saints

Dec 29, 2024 - NFL

Las Vegas Raiders
25 :  10
New Orleans Saints

Dec 15, 2024 - NFL

Washington Commanders
20 :  19
New Orleans Saints

Dec 1, 2024 - NFL

Los Angeles Rams
21 :  14
New Orleans Saints

Nov 17, 2024 - NFL

Cleveland Browns
14 :  35
New Orleans Saints
L L W L L L
Victories

1/6 (17%)

Draw

0/6 (0%)

Defeats

5/6 (83%)

Sep 21, 2025 - NFL

New Orleans Saints
13 :  44
Seattle Seahawks

Jan 5, 2025 - NFL

New Orleans Saints
19 :  27
Tampa Bay Buccaneers

Dec 23, 2024 - NFL

New Orleans Saints
0 :  34
Green Bay Packers

Dec 8, 2024 - NFL

New Orleans Saints
14 :  11
New York Giants

Nov 3, 2024 - NFL

New Orleans Saints
22 :  23
Carolina Panthers

Oct 27, 2024 - NFL

New Orleans Saints
8 :  26
Los Angeles Chargers
Buffalo Bills
Buffalo Bills Latest matches
W W L W W W
Victories

5/6 (83%)

Draw

0/6 (0%)

Defeats

1/6 (17%)

Sep 18, 2025 - NFL

Miami Dolphins
21 :  31
Buffalo Bills

Sep 14, 2025 - NFL

Buffalo Bills
30 :  10
New York Jets

Sep 7, 2025 - NFL

Baltimore Ravens
40 :  41
Buffalo Bills

Jan 26, 2025 - NFL

Buffalo Bills
29 :  32
Kansas City Chiefs

Jan 19, 2025 - NFL

Baltimore Ravens
25 :  27
Buffalo Bills

Jan 12, 2025 - NFL

Denver Broncos
7 :  31
Buffalo Bills
W W W W W W
Victories

6/6 (100%)

Draw

0/6 (0%)

Defeats

0/6 (0%)

Sep 18, 2025 - NFL

Miami Dolphins
21 :  31
Buffalo Bills

Sep 7, 2025 - NFL

Baltimore Ravens
40 :  41
Buffalo Bills

Jan 19, 2025 - NFL

Baltimore Ravens
25 :  27
Buffalo Bills

Jan 12, 2025 - NFL

Denver Broncos
7 :  31
Buffalo Bills

Dec 29, 2024 - NFL

New York Jets
14 :  40
Buffalo Bills

Dec 22, 2024 - NFL

New England Patriots
21 :  24
Buffalo Bills
W L W L L W
Victories

3/6 (50%)

Draw

0/6 (0%)

Defeats

3/6 (50%)

Sep 14, 2025 - NFL

Buffalo Bills
30 :  10
New York Jets

Jan 26, 2025 - NFL

Buffalo Bills
29 :  32
Kansas City Chiefs

Jan 5, 2025 - NFL

Buffalo Bills
16 :  23
New England Patriots

Dec 15, 2024 - NFL

Buffalo Bills
48 :  42
Detroit Lions

Dec 8, 2024 - NFL

Buffalo Bills
42 :  44
Los Angeles Rams

Nov 10, 2024 - NFL

Buffalo Bills
30 :  20
Indianapolis Colts

New Orleans Saints - Buffalo Bills Key Points

  1. New Orleans has allowed 2 touchdowns to running backs this season
  2. New Orleans has allowed an average of 30.0 points per game this season
  3. Buffalo averages 34.0 points per game this season
  4. James Cook has scored 4 touchdowns this season

Our New Orleans Saints vs Buffalo Bills Prediction

Buffalo is a significant favorite in this game; therefore, backing either side on the spread looks to be too risky with how this game could play out. Instead, we will be looking for James Cook to score an anytime touchdown. 

Cook has had an electric start to the season, and as such, he has four touchdowns through the first three weeks. Cook has scored in all three of the Bills' games, that being in Week 1 against the Baltimore Ravens, two in Week 2 against the New York Jets, and one in Week 3 against the Miami Dolphins. 

He is a major part of the Bills’ offense and should find success against a struggling New Orleans side. For that reason, our Buffalo Bills vs New Orleans Saints prediction is: James Cook Anytime Touchdown.

Prediction:

 

James Cook Anytime Touchdown

-175
$400+ offered for betting!

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New Orleans Saints vs Buffalo Bills Picks