New Orleans Saints @ Buffalo Bills 09/28/2025
If you like your Sundays loud and lopsided, circle Buffalo. The Bills return to Highmark Stadium for a Week 4 kickoff against the Saints on Sunday, September 28, 2025, 1:00 PM ET, and the betting angle is as clean as a Josh Allen deep strike. Buffalo comes in undefeated at 3–0, rolling behind a high-octane offense averaging 34 points per game. Even with injuries to Matt Milano and Ed Oliver, the Bills have been efficient on both sides of the ball, and their home scoring clip makes Highmark a dangerous place for any visitor.
The Saints, by contrast, are still searching for traction. Coming off a 44–13 shellacking in Seattle, New Orleans has struggled to generate consistent offense, with Spencer Rattler showing flashes but failing to string together sustained drives. Their defense has been vulnerable to big plays, including a 95-yard punt return last week, and injuries to Chase Young, Dillon Radunz, and Trey Palmer further hamper their ability to keep pace with elite competition.
When these teams last met, Buffalo dominated 31–6 in New Orleans, and early-season form suggests little has changed. With the Bills cruising through their first three games and the Saints reeling, the heavy favorite status is well-earned. For those seeking a more digestible wager than the moneyline, the spread and total present cleaner opportunities, especially given Buffalo’s scoring punch at home and New Orleans’ struggles on both sides of the ball.
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Our betting predictions for the match New Orleans Saints @ Buffalo Bills
Main Tip: Total – Over 47.5 Points
Our primary betting tip: Total — Over 47.5 at -110 with ESPN BET. Highmark has been a friendly stage for points. The Bills’ offense is humming, and while their defense is aggressive, it also invites tempo. The Saints, even in losses, have shown flashes in the passing game that can contribute to the total, especially if they’re forced into chase mode. With Buffalo near the mid-30s per game and the Saints capable of finding late scores, this number is reachable. Over 47.5 at -110 with ESPN BET.
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Tip 2: Spread – Buffalo Bills -16.5
Our secondary betting prediction: Spread — Bills -16.5 at -110 with ESPN BET. Buffalo has been rolling with about 34 points per game overall and 36 at home, which plays into a big-number spread. The Saints are sitting around 17 per game, with protection and rhythm still a work in progress. Buffalo’s balanced punch should set the tone, and if the defense forces early third-and-long scenarios, this can snowball. It’s a big number, but the in-form team at home with a high-scoring average justifies laying the points. Bills -16.5 at -110 with ESPN BET.
Tip 3: Moneyline – Buffalo Bills ML
Our final prediction: Moneyline — Bills ML at (bet365). This is the “don’t overthink it” play. Buffalo’s early-season body of work dwarfs what New Orleans has shown. The Bills are surging at home, the Saints are searching for consistency, and the last direct meeting was a one-way street. The price is hefty, but it reflects reality. If you’re adding a parlay leg or just want the straight winner, Bills ML at best odds (Bet365) is an easy pick.
Team news
Depth charts matter, but so does early-season rhythm. Buffalo has established a fast pace under head coach Sean McDermott—explosive through the air with timely physicality on the ground. New Orleans, under head coach Kellen Moore, is still trying to find the right blend: keeping the pocket clean, generating more consistent early-down success, and tightening coverage on the back end to limit quick-strike drives.
Buffalo Bills performance check
Head coach: Sean McDermott. The Bills’ offense is playing on schedule, averaging about 34 points per game, with the home average even a touch higher. They’ve been particularly sharp in the red zone, and the overall balance—vertical threats paired with a punishing run element—makes it tough to sit in two-high shells all afternoon. On defense, they’re giving up roughly 23.7 per game overall, including some shootout vibes at home, but they create pressure and speed up quarterbacks’ internal clocks.
The last outing—a 31-21 home win over Miami—showed that when needed, Buffalo can grind possessions, win field position, and still hit explosive plays. The situational tackling has improved week over week, and while the unit will give up yards at times, it typically stiffens when the field compresses. Special teams have been clean, flipping the field enough to tilt the momentum. Big picture: Buffalo looks like a top-tier AFC East contender, and this is the kind of spot where they tend to put their foot down.
How is the current performance of the New Orleans Saints
Head coach: Kellen Moore. The Saints are averaging around 17 points per game and allowing about 23, a profile that makes it tough to win if they fall behind early. Protection has been hot-and-cold, and the offense has struggled to string together sustained drives against aggressive fronts. That showed in the most recent outing—an away loss by 31 points in Seattle—where negative scripts forced more obvious passing situations.
The defense still flies to the ball and can be opportunistic, but explosive plays allowed have been costly. The key for New Orleans here: stay ahead of the sticks, lean into quick-game concepts to neutralize pass rush, and let the run game set up manageable second and third downs. If they can generate takeaways, they can compress the scoreboard, but against a team that puts up a mid-30s average at home, a clean four-quarter performance is mandatory.
Statistics
- – Last direct meeting: Bills 31-6 at New Orleans (Buffalo road win)
- – Head-to-Head last 5 (all competitions): Bills 2 wins, Saints 3 wins
- – Form last 5 (all competitions): Bills 4 wins, 1 loss; Saints 0 wins, 4 losses
- – Last match results: – Bills: 31-21 home win vs Miami Dolphins – Saints: 13-44 away loss vs Seattle Seahawks
- – Bills scoring average: about 34.0 per game (home ~36.0); allowed ~23.7 per game (home ~30.5)
- – Saints scoring average: about 17.0 per game; allowed ~23.0 per game
TrustnBet Final Thoughts
The tape and the trends both point in the same direction. Buffalo’s offense is humming at a mid-30s clip; the home environment amplifies that advantage, and New Orleans hasn’t yet shown the four-quarter stability to match score for score. That informs our three angles: lay the points on the spread with Bills -16.5, ride the Over 47.5 given Buffalo’s home scoring profile and Saints’ likely chase mode, and if you want the safest outcome, the Bills moneyline is the straightforward call. Different price tiers, same story: Buffalo’s current form and matchup edges justify the positions.
