Saints vs Bills Prediction — AI Finds CAN'T MISS NFL Lines & Props (Sep 28)
Updated: 2025-09-21T02:28:40.156150ZBy Remi at Leans.AI — AI picks for ATS, ML, OU & props
The New Orleans Saints will travel to Buffalo on September 28, 2025 to face the undefeated Bills in a daunting road test, with New Orleans entering the game as heavy underdogs after a rough 0–3 start. Buffalo will look to extend their dominance at home behind Josh Allen, while the Saints must find some spark offensively to keep this one from getting away early.
Get key insights, betting trends, and AI-powered predictions to help incorporate into your betting strategies.
GAME INFO
Date: Sep 28, 2025
Start Time: 1:00 PM EST
Venue: Highmark Stadium
Bills Record: (3-0)
Saints Record: (0-3)
OPENING ODDS
NO Moneyline: +882
BUF Moneyline: -1587
NO Spread: +15.5
BUF Spread: -15.5
Over/Under: 47.5
NO
Betting Trends
- New Orleans has failed to cover in each of their first three games (0–3 ATS), indicating that they’ve struggled to stay even in matchups where they weren’t the favorites.
BUF
Betting Trends
- Buffalo is 2–1 ATS in 2025 and has a strong home history, frequently covering large spreads at Highmark Stadium.
MATCHUP TRENDS
- The spread is expected to be wide—some odds already show the Saints as 16.5-point underdogs—suggesting this could be the largest line of the season so far. Meanwhile, over/unders in recent Bills games have leaned high, making the total (likely near 48.5) an area to watch.
NO vs. BUF
Best Prop Bet
- Remi's searched hard and found the best prop for this matchup: K. Shakir over 43.5 Receiving Yards.
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New Orleans vs Buffalo Prediction & Odds:
Free NFL Betting Insights for 9/28/25
The Saints, on the other hand, desperately need a spark, as their offense has sputtered behind inconsistent quarterback play and a ground game that has failed to sustain drives; without finding rhythm in short-yardage and third-down situations, New Orleans risks another blowout. Their best chance to compete lies in creativity—using misdirection, quick passes to backs and tight ends, and vertical shots to stretch Buffalo’s defense—but execution must be near flawless to overcome the Bills’ speed and depth. On defense, New Orleans must find ways to pressure Allen while maintaining discipline, a near-impossible task given his ability to extend plays and punish over-aggression. From a betting standpoint, the Bills are heavy favorites with spreads hovering around -16.5, one of the largest lines of the season, a reflection of both Buffalo’s dominance and the Saints’ futility so far. The total sits near 48.5, and given Buffalo’s recent offensive outbursts combined with New Orleans’ defensive lapses, the over could be tempting, though if the Saints offense stalls again, the under may come into play. Ultimately, this game looks like a defining test for New Orleans—either they show resilience and keep it close with smart, disciplined football, or Buffalo continues its early-season steamroll, sending a clear message to the rest of the AFC that the road to the Super Bowl runs through Orchard Park.
Giving back with every point pic.twitter.com/k0JmhMxq5S
— New Orleans Saints (@Saints) September 24, 2025
New Orleans Saints NFL Preview
The New Orleans Saints head into their September 28, 2025 matchup against the Buffalo Bills as heavy underdogs, staring at a daunting 0–3 start and carrying the weight of a blowout 44–13 loss that highlighted their many early-season shortcomings. Offensively, the Saints have struggled to establish rhythm, with protection issues along the offensive line limiting their quarterback’s ability to make reads and leaving the ground game inconsistent at best. To have any chance in Buffalo, New Orleans must lean into creativity—short, quick throws to mitigate pass rush pressure, screens and misdirection plays to get the ball into the hands of playmakers like Alvin Kamara, and occasional vertical shots to stretch the defense and prevent the Bills from loading up the box. The receiving corps has talent, but execution has been sloppy, and penalties have killed drives, making efficiency on early downs an absolute necessity if they hope to sustain possession and keep Josh Allen off the field. Defensively, the Saints face a nightmare assignment against a Buffalo offense that thrives on tempo and big plays, and their margin for error is razor thin; discipline in coverage, gap control against Allen’s scrambling, and opportunistic turnovers are their only realistic tools to keep this from getting out of hand.
The Saints’ secondary must be sharp in communication, as one blown coverage could lead to instant points, and their pass rush must find ways to generate pressure without overcommitting, since Allen punishes broken contain better than almost any quarterback in football. Special teams will also be a factor, as hidden yardage in the return game or a timely field goal might be their best shot at stealing momentum. From a betting perspective, the Saints’ 0–3 ATS record so far underscores their inability to stay competitive in losses, making them a risky proposition for backers despite the wide spread. The total sitting near 48.5 may push bettors toward the over if they expect Buffalo to score at will, but unless the Saints find offensive rhythm, they risk being the reason the game stays under. For New Orleans, the path to even keeping this competitive is narrow—play clean football, win the turnover battle, and string together enough methodical drives to limit Buffalo’s possessions—but given their form to this point, they will need near-perfection just to cover, let alone pull off one of the biggest upsets of the season.
Credit: USA TODAY/IMAGN
Buffalo Bills NFL Preview
The Buffalo Bills enter their September 28, 2025 matchup against the New Orleans Saints with all the momentum of a 3–0 start and the swagger of a team that looks every bit like a Super Bowl contender. At the center of it all is Josh Allen, who continues to dazzle with his dual-threat skill set, stretching defenses vertically with his big arm while keeping them honest with his ability to scramble for chunk gains. The Bills’ offensive line has done a strong job protecting Allen, giving him time to find his versatile group of pass-catchers, and the run game has been efficient enough to keep opponents from keying solely on the passing attack. Against a Saints defense that has been plagued by breakdowns and an inability to hold up in coverage, Buffalo will likely try to set an aggressive tone early, using tempo and explosive plays to seize control before halftime. On the other side of the ball, the Bills’ defense has been opportunistic, feasting on mistakes and collapsing pockets, and they will look to expose a New Orleans offensive line that has struggled in protection and contributed to their 0–3 start.
Expect Buffalo’s pass rush to be relentless, aiming to create turnovers and short fields that can turn a competitive game into a rout. The secondary has also been sharp, with disciplined coverage that makes it difficult for quarterbacks to find rhythm, and against a Saints offense that has yet to find consistency, that edge could prove overwhelming. Special teams remain a quiet strength, with reliable kicking and solid coverage units that help Buffalo win the hidden-yardage battle. From a betting perspective, Buffalo’s 2–1 ATS start combined with their history of covering large spreads at home makes them a formidable favorite, even as they lay one of the biggest lines of the season at -16.5. The total near 48.5 also points toward fireworks, as Buffalo’s offense has shown the capability to push scores high almost single-handedly. Ultimately, this game looks like another chance for the Bills to flex their dominance, showcase their offensive depth, and solidify their place as one of the NFL’s most feared teams, with the home crowd at Highmark Stadium eager to watch their team keep rolling.
Fall ball.@JoshAllenQB | #BillsMafia pic.twitter.com/1vUy7ZXriu
— Buffalo Bills (@BuffaloBills) September 24, 2025
New Orleans vs. Buffalo Prop Picks (AI)
New Orleans vs. Buffalo Prediction (AI)
Remi, our AI sports wizard, has been pouring over exorbitant amounts of data from every past game between the Saints and Bills and using recursive machine learning and cutting-edge AI to examine the data to a single cover probability.
The Algorithm has been most focused on the unproportionally assigned weight knucklehead sportsbettors tend to put on player performance factors between a Saints team going up against a possibly strong Bills team. In reality, the true game analytics appear to reflect a slight lean against one Vegas line in particular.
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Below is our current AI New Orleans vs Buffalo picks, computer picks Saints vs Bills, best bets, model edges, confidence ratings.
| DATE | GAME | LEAN | %WIN | UNITS | LEVEL | |
|---|---|---|---|---|---|---|
| ACTIVE PICKS LOCKED - SEE NOW | ||||||
These picks update as information changes—injury reports, weather, and market movement. Each line shows our model’s fair price, the edge versus the market, and a unit confidence rating (1–10). Odds and availability vary by sportsbook and time. Edges are computed against the listed price; value may change after line moves. Always shop for the best number. See the full NFL Schedule.
Saints Betting Trends
New Orleans has failed to cover in each of their first three games (0–3 ATS), indicating that they’ve struggled to stay even in matchups where they weren’t the favorites.
Bills Betting Trends
Buffalo is 2–1 ATS in 2025 and has a strong home history, frequently covering large spreads at Highmark Stadium.
Saints vs. Bills Matchup Trends
The spread is expected to be wide—some odds already show the Saints as 16.5-point underdogs—suggesting this could be the largest line of the season so far. Meanwhile, over/unders in recent Bills games have leaned high, making the total (likely near 48.5) an area to watch.
New Orleans vs. Buffalo Game Info
What time does New Orleans vs Buffalo start on September 28, 2025?
New Orleans vs Buffalo starts on September 28, 2025 at 1:00 PM EST.
Where is New Orleans vs Buffalo being played?
Venue: Highmark Stadium.
What are the opening odds for New Orleans vs Buffalo?
Spread: Buffalo -15.5
Moneyline: New Orleans +882, Buffalo -1587
Over/Under: 47.5
What are the records for New Orleans vs Buffalo?
New Orleans: (0-3) | Buffalo: (3-0)
What is the AI best bet for New Orleans vs Buffalo?
Remi's searched hard and found the best prop for this matchup: K. Shakir over 43.5 Receiving Yards.. Prices move—always shop for the best number.
What are New Orleans vs Buffalo trending bets?
The spread is expected to be wide—some odds already show the Saints as 16.5-point underdogs—suggesting this could be the largest line of the season so far. Meanwhile, over/unders in recent Bills games have leaned high, making the total (likely near 48.5) an area to watch.
What are New Orleans trending bets?
NO trend: New Orleans has failed to cover in each of their first three games (0–3 ATS), indicating that they’ve struggled to stay even in matchups where they weren’t the favorites.
What are Buffalo trending bets?
BUF trend: Buffalo is 2–1 ATS in 2025 and has a strong home history, frequently covering large spreads at Highmark Stadium.
Where can I find AI Picks for New Orleans vs Buffalo?
See our latest NFL picks and odds pages for 2025 to compare prices before you bet.
New Orleans vs. Buffalo Odds
AI algorithm Remi is pouring through mountains of data points on each line. In fact, anytime the New Orleans vs Buffalo trends are analyzed, there’s always several intriguing angles to key in on. Not to mention games played at extreme temps can often follow normal, predictable patterns.
New Orleans vs Buffalo Opening Odds
NO Moneyline:
+882 BUF Moneyline: -1587
NO Spread: +15.5
BUF Spread: -15.5
Over/Under: 47.5
New Orleans vs Buffalo Live Odds
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|---|---|---|---|---|---|
|
Oct 30, 2025 8:15PM EDT
Baltimore Ravens
Miami Dolphins
10/30/25 8:15PM
Ravens
Dolphins
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–
–
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-420
+330
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-7.5 (-115)
+7.5 (-105)
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O 51.5 (-105)
U 51.5 (-115)
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Nov 2, 2025 1:00PM EST
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Cincinnati Bengals
11/2/25 1PM
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–
–
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-154
+130
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-3 (-102)
+3 (-120)
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O 50.5 (-118)
U 50.5 (-104)
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Nov 2, 2025 1:00PM EST
Indianapolis Colts
Pittsburgh Steelers
11/2/25 1PM
Colts
Steelers
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–
–
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-158
+134
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-3 (-115)
+3 (-105)
|
O 50.5 (-104)
U 50.5 (-118)
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Nov 2, 2025 1:00PM EST
Carolina Panthers
Green Bay Packers
11/2/25 1PM
Panthers
Packers
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–
–
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+700
-1100
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+13.5 (-108)
-13.5 (-112)
|
O 44.5 (-105)
U 44.5 (-115)
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Nov 2, 2025 1:00PM EST
Atlanta Falcons
New England Patriots
11/2/25 1PM
Falcons
Patriots
|
–
–
|
+194
-235
|
+5.5 (-115)
-5.5 (-105)
|
O 44.5 (-110)
U 44.5 (-110)
|
|
|
Nov 2, 2025 1:00PM EST
Denver Broncos
Houston Texans
11/2/25 1PM
Broncos
Texans
|
–
–
|
+102
-120
|
+1.5 (-108)
-1.5 (-112)
|
O 39.5 (-110)
U 39.5 (-110)
|
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|
Nov 2, 2025 1:00PM EST
San Francisco 49ers
New York Giants
11/2/25 1PM
49ers
Giants
|
–
–
|
-148
+126
|
-2.5 (-115)
+2.5 (-105)
|
O 48.5 (-115)
U 48.5 (-105)
|
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Nov 2, 2025 1:00PM EST
Los Angeles Chargers
Tennessee Titans
11/2/25 1PM
Chargers
Titans
|
–
–
|
-480
+370
|
-9.5 (-110)
+9.5 (-110)
|
O 43.5 (-105)
U 43.5 (-115)
|
|
|
Nov 2, 2025 1:00PM EST
Minnesota Vikings
Detroit Lions
11/2/25 1PM
Vikings
Lions
|
–
–
|
+370
-480
|
+8.5 (-108)
-8.5 (-112)
|
O 48.5 (-110)
U 48.5 (-110)
|
|
|
Nov 2, 2025 4:05PM EST
New Orleans Saints
Los Angeles Rams
11/2/25 4:05PM
Saints
Rams
|
–
–
|
+730
-1150
|
+14.5 (-115)
-14.5 (-105)
|
O 43.5 (-110)
U 43.5 (-110)
|
|
|
Nov 2, 2025 4:05PM EST
Jacksonville Jaguars
Las Vegas Raiders
11/2/25 4:05PM
Jaguars
Raiders
|
–
–
|
-158
+134
|
-3 (-105)
+3 (-115)
|
O 44.5 (-115)
U 44.5 (-105)
|
|
|
Nov 2, 2025 4:25PM EST
Kansas City Chiefs
Buffalo Bills
11/2/25 4:25PM
Chiefs
Bills
|
–
–
|
-134
+114
|
-1.5 (-114)
+1.5 (-106)
|
O 52.5 (-105)
U 52.5 (-115)
|
|
|
Nov 2, 2025 8:20PM EST
Seattle Seahawks
Washington Commanders
11/2/25 8:20PM
Seahawks
Commanders
|
–
–
|
-166
+140
|
-3 (-110)
+3 (-110)
|
O 47.5 (-112)
U 47.5 (-108)
|
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|
Nov 3, 2025 8:15PM EST
Arizona Cardinals
Dallas Cowboys
11/3/25 8:15PM
Cardinals
Cowboys
|
–
–
|
+128
-152
|
+2.5 (-104)
-2.5 (-118)
|
O 53.5 (-110)
U 53.5 (-110)
|
|
|
Nov 6, 2025 8:15PM EST
Las Vegas Raiders
Denver Broncos
11/6/25 8:15PM
Raiders
Broncos
|
–
–
|
+370
-480
|
+9.5 (-115)
-9.5 (-105)
|
O 42.5 (-120)
U 42.5 (-102)
|
|
|
Nov 9, 2025 9:30AM EST
Atlanta Falcons
Indianapolis Colts
11/9/25 9:30AM
Falcons
Colts
|
–
–
|
+290
-360
|
+7 (-105)
-7 (-115)
|
O 48.5 (-108)
U 48.5 (-112)
|
NFL Past Picks
Remi—our in-house AI—prices every game and prop using multi-season priors, tempo/efficiency, injury/usage signals, and market movement.
We publish fair prices, recommended “buy-to” numbers, and confidence so you can bet prices, not teams.
This preview covers New Orleans Saints vs. Buffalo Bills on September 28, 2025 at Highmark Stadium.
Odds shown reflect widely available numbers and may update closer to kickoff.
Want more? Check live edges, player props, and line moves on our NFL odds pages, and compare prices before you place a bet.
| LEAN | %WIN | UNITS | RESULT | |
|---|---|---|---|---|
| TB@NO | TB -3.5 | 52.3% | 1 | WIN |
| GB@PIT | GB -2.5 | 52.3% | 1 | WIN |
| SF@HOU | SF +2.5 | 56.0% | 6 | LOSS |
| NYG@PHI | NYG +7.5 | 53.9% | 3 | LOSS |
| BUF@CAR | CAR +7.5 | 54.2% | 3 | LOSS |
| DAL@DEN | DAL +3.5 | 55.0% | 4 | LOSS |
| MIA@ATL | MIA +7 | 54.3% | 4 | WIN |
| CLE@NE | CLE +7 | 56.8% | 6 | LOSS |
| TB@NO | BAKER MAYFIELD OVER 15.5 RUSH YDS | 56.6% | 6 | LOSS |
| MIN@LAC | JUSTIN HERBERT PASS ATT UNDER 35.5 | 55.5% | 5 | WIN |
| TB@DET | TB +6.5 | 54.4% | 4 | LOSS |
| TB@DET | RACHAAD WHITE UNDER 14.5 RUSH ATT | 54.4% | 4 | WIN |
| NE@TEN | NE -6.5 | 55.2% | 5 | WIN |
| CAR@NYJ | CAR -110 | 57.4 | 4 | WIN |
| PHI@MIN | PHI -130 | 58.0% | 6 | WIN |
| GB@ARI | ARI +7 | 54.8% | 5 | WIN |
| NO@CHI | NO +4.5 | 57.4% | 7 | LOSS |
| WAS@DAL | JAYDEN DANIELS 1H RUSH YDS OVER 22.5 | 56.1% | 5 | WIN |
| GB@ARI | JORDAN LOVE 1Q PASS YDS OVER 54.5 | 56.6% | 6 | WIN |
| PIT@CIN | JONNU SMITH RECEPTIONS OVER 3.5 | 55.3% | 5 | LOSS |
| BUF@ATL | BUF -3.5 | 54.7% | 4 | LOSS |
| CHI@WAS | JAYDEN DANIELS OVER 1.5 PASS TDS | 56.6% | 6 | WIN |
| TEN@LV | UNDER 42 | 54.8% | 3 | WIN |
| DET@KC | DET +2.5 | 55.7% | 7 | LOSS |
| SEA@JAC | SEA -112 | 55.7% | 5 | WIN |
| LAC@MIA | LAC -3.5 | 54.0% | 3 | LOSS |
| ARI@IND | IND -8.5 | 55.6% | 5 | LOSS |
| TEN@LV | TEN +4.5 | 56.7% | 6 | LOSS |
| LAR@BAL | LAR -7 | 56.2% | 6 | WIN |
| SF@TB | SF +3.5 | 57.2% | 7 | LOSS |
| CLE@PIT | JAYLEN WARREN UNDER 46.5 RUSH YDS | 54.4% | 4 | LOSS |
| DEN@NYJ | BREECE HALL OVER 26.5 RECV YDS | 55.0% | 4 | LOSS |
| KC@JAC | UNDER 45.5 | 54.9% | 3 | LOSS |
| KC@JAC | PATRICK MAHOMES UNDER 23.5 PASS COMP | 56.6% | 6 | LOSS |
| HOU@BAL | HOU -125 | 58.5% | 7 | WIN |
| DET@CIN | DET -10 | 55.6% | 5 | WIN |
| DAL@NYJ | NYJ +1.5 | 53.7% | 3 | LOSS |
| TB@SEA | TB +3.5 | 54.9% | 4 | WIN |
| TEN@ARI | ARI -7 (BUY 0.5) | 54.9% | 4 | LOSS |
| DEN@PHI | DEN +4.5 | 57.5% | 7 | WIN |
| MIA@CAR | TETAIROA MCMILLAN OVER 58.5 RECV YDS | 54.5% | 4 | WIN |
| LV@IND | ASHTON JEANTY UNDER 67.5 RUSH YDS | 54.4% | 4 | WIN |
| SF@LAR | DEMARCUS ROBINSON OVER 29.5 RECV YDS | 55.7% | 5 | WIN |
| NYJ@MIA | NYJ +3 | 53.8 | 3 | LOSS |
| CIN@DEN | DEN -7.5 | 54.8 | 4 | WIN |
| NYJ@MIA | OVER 44 | 52.9% | 2 | WIN |
| CIN@DEN | UNDER 44.5 | 53.7% | 3 | WIN |
| NYJ@MIA | GARRETT WILSON UNDER 9 TARGETS | 53.7% | 3 | WIN |
| CIN@DEN | TEE HIGGINS OVER 6.5 RECV TARGETS | 55.5% | 5 | LOSS |
| WAS@ATL | ATL -2.5 | 54.3 | 4 | WIN |
| BAL@KC | BAL -2.5 | 56.3% | 6 | LOSS |