Bills vs Saints Prediction 9/28/25 NFL Picks Today

The New Orleans Saints and the Buffalo Bills meet in week 4 NFL action from Highmark Stadium on Sunday. We will look at this from a betting perspective and determine the best bets for this game. Here’s a Bills vs Saints Prediction.

New Orleans Saints Recap

The New Orleans Saints come into this game looking to bounce back from their 44-13 loss at the hands of Seattle last time out to sit at 0-3 this season. After this game, New Orleans will head home for a game against the New York Giants.

Saints Looking For Huge Upset For First Win

Spencer Rattler has thrown for 639 yards, 4 touchdowns and an interception on 67.2% passing while Alvin Kamara has 186 rushing yards and a touchdown to lead the Saints on the ground. Juwan Johnson has a team-high 176 receiving yards with a touchdown on 19 receptions while Chris Olave has a team-high 23 catches for 165 yards and Rashid Shaheed’s added 127 receiving yards and a TD as well. On defense, Demario Davis has a team-high 31 total tackles while Carl Granderson leads New Orleans with 3.5 sacks. 

Why the New Orleans Saints will win

• Justin Reid’s team has won each of its last six games with him playing against Josh Palmer.
• The Saints have covered the spread in each of their last 12 games played as underdogs on the East Coast.
• The Bills have failed to cover the spread in six of their last eight home games against NFC opponents.

New Orleans Saints Player Prop Facts

• Alvin Kamara has scored a touchdown in six of his last seven appearances against AFC East opponents.
• Alvin Kamara has recorded 80+ rushing yards in each of the Saints’ last four road games against AFC East opponents.
• Spencer Rattler has recorded 207+ passing yards in each of the Saints’ last five games.
• Spencer Rattler has recorded 25+ completions in each of the Saints’ last four games.
• Brandin Cooks has recorded 19+ rushing and receiving yards in each of his 22 previous appearances with the Saints as underdogs.
• Brandin Cooks has recorded 19+ receiving yards in each of his 22 previous appearances with the Saints as underdogs.
• Heading into Week 4, Chris Olave has the most targets without a receiving touchdown this season (37).

Buffalo Bills Recap

The Buffalo Bills come into this one looking to add on to their 31-21 win over the Miami Dolphins last time out to sit at 3-0 this season. After this game, the Bills will take on the New England Patriots in an AFC East matchup at home.

Bills Looking To Remain Unbeaten

Josh Allen has thrown for 755 yards and 5 touchdowns on 69.7% passing while also rushing for 114 yards and 2 scores. James Cook has a team-high 284 rushing yards and 4 touchdowns while Keon Coleman has a team-high 14 catches for 158 yards and a touchdown. Dalton Kincaid has 13 catches for 151 yards while Khalil Shakir and Josh Palmer each have 100+ receiving yards as well for Buffalo this season. On defense, Christian Benford leads the Bills with 15 total tackles while the Bills’ defense as a whole has combined for 6 sacks and an interception so far this season.

Why the Buffalo Bills will win

• The Bills have won each of their last 15 home games against opponents on a losing streak.
• The Saints have lost each of their last seven games.
• The Saints have failed to cover the spread in seven of their last eight September games against AFC opponents.
• The Bills have covered the spread in each of their last four Sunday home games.

Buffalo Bills Player Prop Facts

• Josh Allen has scored two or more touchdowns in four of the Bills’ last five games against NFC opponents.
• Josh Allen has recorded 22+ completions in nine of the Bills’ last 10 September home games.
• James Cook has recorded 100+ rushing yards in four of the Bills’ last five games as home favorites.
• Josh Allen has recorded 263+ passing yards in eight of the Bills’ last 10 September home games.
• James Cook has scored at least one touchdown in each of the Bills’ last eight games played as favorites on the East Coast.
• Curtis Samuel has recorded 22+ receiving yards in eight of his last nine September home appearances.
• Curtis Samuel has recorded 22+ rushing and receiving yards in nine of his last 10 September home appearances.
• Heading into Week 4, James Cook ranks T1st in the NFL in touchdowns (4) this season.

Total Points Facts

• Each of the Bills’ last seven home games in September have gone OVER the total points line.
• Seven of the Saints’ last eight road games against AFC opponents have gone UNDER the total points line.
• Nine of the last 12 Sunday games at Highmark Stadium have gone OVER the total points line.

Bills vs Saints Prediction

I’m leaning towards New Orleans and the points here. We’re still early enough in the season that a road trip to Buffalo won’t affect a dome team as much as it would in December. While New Orleans got throttled by Seattle, they’ve been somewhat competitive early on, and Buffalo already didn’t cover as a double-digit favorite last week. A 31-17 win for the Bills, which is totally believable, still gets us to the pay window with New Orleans, so give me the Saints and the points here.